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J Appl Physiol 102: 978-984, 2007. First published November 22, 2006; doi:10.1152/japplphysiol.00921.2006
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Dependence of changes in beta-adrenoceptor signal transduction on type and stage of cardiac hypertrophy

Rajat Sethi,1 Harjot K. Saini,2 Xiaobing Guo,2 Xi Wang,2 Vijayan Elimban,2 and Naranjan S. Dhalla2

1Irma Lerma Rangel College of Pharmacy, Department of Pharmaceutical Sciences, Texas A & M University Health Sciences Center, Kingsville, Texas; and 2Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

Submitted 21 August 2006 ; accepted in final form 16 November 2006


   ABSTRACT
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 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
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To examine whether cardiac hypertrophy is associated with changes in beta-adrenoceptor signal transduction mechanisms, pressure overload (PO) was induced by occlusion of the abdominal aorta and volume overload (VO) by creation of an aortocaval shunt for 4 and 24 wk in rats. After hemodynamic assessment of the animals, the left ventricular (LV) particulate fraction was isolated for measurement of beta1-adrenoceptors and adenylyl cyclase activity, and cardiomyocytes were isolated for monitoring of the intracellular Ca2+ concentration. Although PO and VO produced cardiac hypertrophy and increased LV end-diastolic pressure at 4 wk, cardiac function was increased in animals subjected to PO but remained unaltered in animals subjected to VO. Cardiac hypertrophy and increased LV end-diastolic pressure were associated with depressed cardiac function at 24 wk of PO or VO, but clinical signs of congestive heart failure were evident only in animals subjected to VO. Isoproterenol-induced increases in cardiac function, activation of adenylyl cyclase activity, and increase in intracellular Ca2+ concentration, as well as beta1-adrenoceptor density, were unaltered by PO at 4 wk, augmented by VO at 4 wk, and attenuated by PO and VO at 24 wk. These results suggest that alterations in beta1-adrenoceptor signal transduction are dependent on the type and stage of cardiac hypertrophy.

pressure overload; volume overload; cardiac function; beta-adrenoceptors; adenylyl cyclase; intracellular calcium concentration

IT IS WELL ESTABLISHED that beta-adrenoceptor activation stimulates adenylyl cyclase activity through the participation of G proteins and promotes the formation of cAMP in the myocardium (1, 3, 10, 38). The elevated level of cAMP increases the intracellular concentration of Ca2+ ([Ca2+]i) in cardiomyocytes on protein kinase A-mediated phosphorylation of different Ca2+-handling proteins in the membrane and produces the positive inotropic effect in the heart (1, 3, 10, 38). This beta-adrenoceptor-mediated signal transduction mechanism not only regulates the contractile activity of the healthy heart, but it is also considered to provide critical support for the maintenance of cardiac function during the development of heart failure (1, 3, 10, 28). Although varying degrees of defects in the beta-adrenoceptor-mediated signal transduction mechanisms have been observed in the failing heart at terminal stages (2, 4, 17, 28, 39), it has been reported that these events in different types of heart failure are unaltered, upregulated, or downregulated (19, 31–33, 43, 44). Since cardiac hypertrophy is invariably associated with heart failure (16, 45), it is possible that the conflicting results regarding changes in beta-adrenoceptor-mediated mechanisms during the development of heart failure are due to differences in the type and stage of hypertrophied failing hearts. Accordingly, this study was undertaken to test whether alterations in beta-adrenoceptor signal transduction in cardiac hypertrophy due to pressure overload (PO) are different from those due to volume overload (VO). PO is known to induce the concentric form of cardiac hypertrophy (6, 8, 25), whereas VO has been shown to produce the eccentric form of cardiac hypertrophy (6, 8, 42).


   METHODS
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 METHODS
RESULTS
 DISCUSSION
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Experimental model and hemodynamic assessment.   All protocols for experiments were approved by the University of Manitoba Animal Care Committee in accordance with the guidelines of the Canadian Council on Animal Care. Male Sprague-Dawley rats weighing 175–200 g each were used in the study. Cardiac hypertrophy due to PO was induced by 4 and 24 wk of abdominal aorta occlusion, as described earlier (6). Cardiac hypertrophy due to VO was induced by creation of an aortocaval shunt for 4 and 24 wk, as described previously (6, 42). The selection of 4- and 24-wk periods for PO and VO is based on our experience with these experimental models for the induction of early (compensated) and late (decompensated) stages of cardiac hypertrophy, respectively. Sham-operated rats for each group were used as controls. In one set of experiments, 12 animals for each PO or VO group were anesthetized with an intraperitoneal injection of a mixture of ketamine (90 mg/kg) and xylazine (10 mg/kg). These animals were assessed hemodynamically with a microtipped pressure transducer (model SPR-249, Millar Instruments, Houston, TX). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate of change of pressure development (+dP/dt), and rate of change of pressure decay (–dP/dt) were recorded. Left ventricular developed pressure (LVDP) was calculated as LVSP – LVEDP. The heart, lung, and liver weights, beta-adrenoceptor binding parameters, adenylyl cyclase activity, and effect of isoproterenol on [Ca2+]i in cardiomyocytes isolated from these hearts were determined. The second set of experiments was carried out on four animals in each PO or VO group to investigate the isoproterenol-mediated changes in LVDP.

Isoproterenol-induced changes in cardiac function.   To assess the effect of isoproterenol on cardiac function under controlled conditions, hearts from PO and VO, as well as sham, animals were isolated and perfused with oxygenated Krebs-Henseleit solution containing 1.25 mM Ca2+ at 37°C according to the technique used previously (42, 44). The hearts were paced electrically at 300 beats/min, and the coronary flow was maintained at 10 ml/min. Isoproterenol (1 µM) was infused into the perfusion stream, and the positive inotropic effect was measured at the peak point.

Determination of beta-adrenoceptor binding characteristics and adenylyl cyclase activity.   Crude membrane fraction, isolated from the left ventricle (43, 44), was employed for the beta-adrenoceptor binding and adenylyl cyclase studies. Specific binding of [125I]iodocyanopindolol was determined as a difference between binding values in the absence or presence of CGP-20712A, a selective beta1-adrenoceptor antagonist, as described earlier (44). The binding characteristics for beta1-adrenoceptor, maximal binding (Bmax) and dissociation constant (Kd), were calculated by the Scatchard plot analysis using the interactive LIGAND program. The adenylyl cyclase activity was measured by determining the formation of [32P]cAMP from [{alpha}-32P]ATP, as described previously (43). The reaction mixture contained 10 µM GTP and 0.3% ascorbic acid for study of the adenylyl cyclase activity in the absence and presence of isoproterenol (100 µM).

Measurement of [Ca2+]i in cardiomyocytes.   Purified cardiomyocytes were isolated from the left ventricle according to the procedure described earlier (30). The cardiomyocytes were loaded with fura 2-AM, washed, and incubated with and without isoproterenol (100 µM) for 5 min. [Ca2+]i was measured in the absence and presence of 30 mM KCl, a known depolarizing agent, using spectrofluorometry, as described previously (30). The KCl-induced increase in [Ca2+]i was calculated as the net increase above the basal value, whereas the isoproterenol-induced increase in [Ca2+]i was calculated by subtraction of KCl-induced values in the absence of isoproterenol from those in the presence of isoproterenol.

Statistical analysis.   Values are means ± SE. The difference between control and experimental groups was evaluated statistically by one-way ANOVA followed by the Newman-Keuls test. Differences were considered significant at P < 0.05.


   RESULTS
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General characteristics and hemodynamic changes.   The data in Table 1 describe the general characteristics of animals subjected to 4 and 24 wk of PO or VO. Heart weight and heart weight-to-body weight ratio at 4 and 24 wk of PO or VO were significantly increased compared with the respective values of the sham control animals. Increases in these parameters indicated a higher degree of cardiac hypertrophy in VO than in PO animals. No change in lung weight or liver enlargement was seen in PO animals. VO animals showed an increase in lung weight and no changes in liver weight at 4 wk but an increase in lung and liver weights at 24 wk (Table 1). In contrast to 4 and 24 wk of PO and 4 wk of VO, breathing difficulty and sluggish movement, in addition to the clinical signs of congestive heart failure, such as edema and pleural effusion, were noted at 24 wk of VO.


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  		Table 1. General characteristics at 4 and 24 wk of PO or VO in rats

 
PO and VO animals were assessed hemodynamically, and the results are given in Figs. 1 and 2, respectively. At 4 wk of PO, LVDP, LVEDP, +dP/dt, and –dP/dt were significantly increased by 10 ± 3.9%, 241 ± 7.9%, 28 ± 5.8%, and 25 ± 5.2%, respectively; at 24 wk of PO, LVDP, +dP/dt, and –dP/dt were depressed by 43 ± 3.9%, 28 ± 5.3%, and 31 ± 5.7%, respectively, but LVEDP was elevated (291 ± 2.4%; Fig. 1). At 4 wk of VO, no changes in LVDP, +dP/dt, and –dP/dt were apparent, whereas LVEDP was significantly increased (276 ± 12.8%; Fig. 2). At 24 wk of VO, a marked increase in LVEDP (365 ± 10.2%) was associated with a significant decrease in LVDP, +dP/dt, and –dP/dt: 50 ± 4.9%, 31 ± 2.8%, and 39 ± 2.3%, respectively (Fig. 2).


Figure 1
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  		Fig. 1. Left ventricular (LV) function in rats in which pressure overload (PO) was induced by abdominal aorta occlusion for 4 and 24 wk. A: LV developed pressure [LVDP = LV systolic pressure – LV end-diastolic pressure (LVEDP)] in sham and PO animals. B: LVEDP in sham and PO animals. C: rate of change of pressure development (+dP/dt) in sham and PO animals. D: rate of change of pressure decay (–dP/dt) in sham and PO animals. Values are means ± SE of 12 animals in each group. *P < 0.05 vs. respective sham.

 

Figure 2
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  		Fig. 2. LV function in rats in which volume overload (VO) was induced by aortocaval shunt for 4 and 24 wk. A: LVDP in sham and VO animals. B: LVEDP in sham and VO animals. C: +dP/dt in sham and VO animals. D: –dP/dt in sham and VO animals. Values are means ± SE of 12 animals in each group. *P < 0.05 vs. respective sham.

 
Positive inotropic effect of isoproterenol.   Changes in the inotropic effect of isoproterenol were examined by infusion of isoproterenol into the perfusion stream; the results (i.e., its peak action on LVDP) are given in Fig. 3. Isoproterenol produced positive inotropic action in sham control, as well as PO and VO, hearts. However, at 4 wk of PO, the magnitude of the positive inotropic effect of isoproterenol was not different from the control (122 ± 10.2% and 106 ± 8.3%, respectively) but was markedly attenuated at 24 wk (100 ± 5.10% and 56 ± 3.7%, respectively; Fig. 3). The positive inotropic action of isoproterenol was augmented at 4 wk (260 ± 12.9% vs. 103 ± 7.2%) but markedly depressed at 24 wk (38 ± 2.7% vs. 89 ± 6.8%) of VO (Fig. 3). In contrast to 4 wk of PO or VO, at 24 wk of PO or VO, LVDP in the isolated heart preparations was significantly depressed (Fig. 3). Since the increase in LVDP from hearts at 4 wk of PO was not evident in the isolated preparations, in contrast to in vivo conditions, the differences between in vivo and in vitro preparations at this stage of cardiac hypertrophy may be due to washout of different humoral and growth factors circulating in the body on perfusion of the isolated hearts. Further studies in which these factors are inhibited and their in vivo and in vitro effects are compared are needed to understand such differences.


Figure 3
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  		Fig. 3. Effect of isoproterenol (Iso) on cardiac performance of isolated hearts at 4 and 24 wk of PO (A) or VO (B) in rats. Values are means ± SE of 4 hearts in each group. Iso (1 µM) was infused through perfusion stream for maximal response. Expt, PO or VO animals. *P < 0.05 vs. respective –Iso. #P < 0.05 vs. respective sham (Sh).

 
Changes in beta-adrenoceptors and adenylyl cyclase.   The data in Table 2 show that PO induced no change in Bmax or affinity (1/Kd) for beta1-adrenoceptors at 4 wk, whereas Bmax was decreased without any change in the affinity at 24 wk. VO induced a marked increase in Bmax at 4 wk and a decrease at 24 wk, with no change in the affinity of beta1-adrenoceptors (Table 2). Although isoproterenol increased adenylyl cyclase activity at 4 and 24 wk in sham control and PO animals, the activation of adenylyl cyclase by isoproterenol was unaltered at 4 wk but depressed at 24 wk of PO (Table 3). The adenylyl cyclase activity in the absence of isoproterenol at 24 wk of PO was also less than the respective control value. Furthermore, the activation of adenylyl cyclase by isoproterenol was augmented at 4 wk and depressed at 24 wk of VO (Table 3). The adenylyl cyclase activity in the absence of isoproterenol at 4 and 24 wk of VO was not different from the respective control value.


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  		Table 2. Bmax and Kd values for beta1-adrenoceptors in left ventricles at 4 and 24 wk of PO or VO in rats

 

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  		Table 3. Adenylyl cyclase activities in the absence and presence of isoproterenol in left ventricles at 4 and 24 wks of PO or VO in rats

 
Isoproterenol-induced changes in [Ca2+]i in cardiomyocytes.   Alterations in [Ca2+]i in the absence and presence of isoproterenol were studied in quiescent and KCl-depolarized cardiomyocytes at 4 and 24 wk of PO and VO, and the results are shown in Figs. 4 and 5, respectively. At 4 and 24 wk of PO or VO, isoproterenol had no effect on basal [Ca2+]i but enhanced the KCl-mediated increase in [Ca2+]i: 77 ± 2.7% at 4 wk in sham animals and 86 ± 3.8% at 4 wk of PO, 66 ± 3.7% at 24 wk in sham animals and 70 ± 2.1% at 24 wk of PO, 57 ± 2.6% at 4 wk in sham animals and 103 ± 8.9% at 4 wk of VO, and 55 ± 3.8% at 24 wk in sham animals and 43 ± 1.9% at 24 wk of VO (Figs. 4 and 5). Although in cardiomyocytes isolated from PO hearts the KCl-induced increase in [Ca2+]i at 24 wk, unlike that at 4 wk, was decreased, in cardiomyocytes at 4 and 24 wk of VO the KCl-induced increase in [Ca2+]i was depressed (Figs. 4 and 5). However, the isoproterenol-mediated increase in [Ca2+]i was unaltered at 4 wk of PO but depressed by 44 ± 2.1% at 24 wk of PO compared with the respective values for the sham control group (Fig. 4). On the other hand, the isoproterenol-mediated increase in [Ca2+]i was augmented by 51 ± 2.8% at 4 wk of VO and depressed by 128 ± 9.8% at 24 wk of VO (Fig. 5).


Figure 4
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  		Fig. 4. Iso-induced increase in intracellular Ca2+ concentration ([Ca2+]i) in KCl (30 mM)-depolarized cardiomyocytes from LV at 4 and 24 wk of PO in rats. A: basal [Ca2+]i in the presence and absence of Iso. B: KCl-induced increase in [Ca2+]i in the presence and absence of Iso. C: effect of Iso on [Ca2+]i. Values are means ± SE of 4 animals in each group. Cardiomyocytes were treated in the absence or presence of 100 µM Iso for 3 min before [Ca2+]i was measured. Increase in [Ca2+]i due to Iso was calculated by subtracting KCl-induced [Ca2+]i in cardiomyocytes without Iso from that in Iso-treated preparations. *P < 0.05 vs. respective –Iso. #P < 0.05 vs. respective Sh.

 

Figure 5
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  		Fig. 5. Iso-induced increase in [Ca2+]i in KCl (30 mM)-depolarized cardiomyocytes from LV at 4 and 24 wk of VO by aortocaval shunt (AVS) in rats. A: basal [Ca2+]i in the presence and absence of Iso. B: KCl-induced increase in [Ca2+]i in the presence and absence of Iso. C: effect of Iso on [Ca2+]i. Values are means ± SE of 4 animals in each group. Cardiomyocytes were treated and increase in [Ca2+]i was calculated as described in Fig. 4 legend. *P < 0.05 vs. respective –Iso. #P < 0.05 vs. respective Sh.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
In this study, we have shown that cardiac hypertrophy, as reflected by increased heart weight and heart weight-to-body weight ratio, was associated with an increase in cardiac function, as reflected by increased LVDP, +dP/dt, and –dP/dt, at 4 wk of PO. On the other hand, cardiac hypertrophy at 4 wk of VO was associated with unaltered cardiac function. Since LVEDP was increased at 4 wk of PO and VO, it is likely that the development of cardiac hypertrophy at this early stage of PO and VO may be a consequence of increased ventricular wall tension. This view is supported by the association of increased heart weight with the greater increase in LVEDP at 24 wk than at 4 wk of PO or VO. Also, no changes in lung weight or liver weight were observed at 4 and 24 wk of PO, whereas lung weight was increased at 4 and 24 wk of VO and liver weight was increased at 24 wk of VO. In addition, clinical signs of congestive heart failure induced by PO are different from those at 24 wk of VO. These differences between PO and VO animals are in agreement with numerous reports showing varying degrees of alterations in general characteristics and heart function in these experimental models of cardiac remodeling (9, 12, 14, 20, 24). Such differences in cardiac function at the early stages of cardiac hypertrophy may be due to the development of concentric and eccentric types of cardiac hypertrophy in PO and VO animals, respectively (6–8, 22, 27). Although changes in shape and size of cardiomyocytes (cardiac remodeling) are considered to represent a major mechanism of cardiac dysfunction (5, 21), cardiac hypertrophy has been reported to be associated with unaltered, enhanced, or depressed heart function (8, 14, 16, 45). Such findings are consistent with our observations that cardiac function was depressed in hypertrophied hearts at 24 wk of PO or VO, unaltered in hypertrophied hearts at 4 wk of VO, and augmented in hypertrophied hearts at 4 wk of PO. The development of cardiac hypertrophy is an adaptive phenomenon to maintain cardiac function during early stages but may result in cardiac dysfunction at late stages of stress on the heart (5, 14, 16, 21).

In view of the activation of the sympathetic nervous and renin-angiotensin systems, as well as increased formation of growth factors on induction of PO and VO (11, 15, 16, 22, 29), it appears that compensated and decompensated forms of cardiac hypertrophy may depend on the duration of exposure of the heart to different humoral and other growth factors circulating in the body. For the purpose of comparison, we believe that animals subjected to 4 and 24 wk of PO or VO are at compensated and decompensated stages of cardiac hypertrophy, respectively; however, there are marked differences between the PO and VO models of cardiac hypertrophy with respect to cardiac function. Preliminary experiments in our laboratory have indicated that cardiac function in hypertrophied hearts due to PO begins to decline at ~6 wk, whereas no clinical signs of congestive heart failure were evident at 48 wk of PO in rats. On the other hand, in rat hearts in which hypertrophy was induced by VO, cardiac function declined at 10 wk, and clinical signs of congestive heart failure become apparent at 12 wk. Thus extensive studies over different periods of PO- or VO-induced cardiac hypertrophy are needed to understand the molecular and cellular basis of cardiac dysfunction.

The results presented in this study indicate that beta-adrenoceptor-mediated signal transduction mechanisms are unaltered or upregulated in the compensated stages of cardiac hypertrophy and are downregulated in the decompensated stages of cardiac hypertrophy. This view is based on our observations that the positive inotropic effect of isoproterenol, beta1-adrenoceptor density, stimulation of adenylyl cyclase activity by isoproterenol, and isoproterenol-induced increase in [Ca2+]i were unaltered at 4 wk of PO but were augmented at 4 wk of VO. Furthermore, the number of beta1-adrenoceptors, as well as the increase in contractile activity of the heart, stimulation of adenylyl cyclase activity, and increase in [Ca2+]i in cardiomyocytes mediated by isoproterenol, were attenuated at 24 wk of PO or VO. Earlier studies showed an increase in beta1-adrenoceptor density, as well as an augmentation of the isoproterenol-induced increase in adenylyl cyclase activity and contractile force development, at 16 wk of VO in rats (43, 44). A PO-induced increase in beta-adrenoceptor density at early stages of cardiac hypertrophy has also been reported in rats and guinea pigs (15, 18). On the other hand, depression of the density of beta1-adrenoceptors, as well as an isoproterenol-induced increase in cardiac contraction and stimulation of adenylyl cyclase activity, has been observed in dogs with PO-induced congestive heart failure (13, 40, 41). Thus it appears that the time course for the development of cardiac dysfunction, as well as occurrence of changes in beta-adrenoceptor signal transduction mechanisms, in PO-induced cardiac hypertrophy is different from that in VO-induced cardiac hypertrophy.

A detailed investigation employing cardiomyopathic hamsters at different stages of heart failure has indicated that beta1-adrenoceptor density and isoproterenol-induced stimulation of adenylyl cyclase activity were increased at early stages and decreased at late stages of congestive heart failure (19, 31, 34). Since varying degrees of cardiac hypertrophy were evident in all studies indicated above, it appears that alterations in beta-adrenoceptor signal transduction are dependent on the type and stage of the cardiac hypertrophy in different experimental models of heart failure. Furthermore, upregulation of beta-adrenoceptor mechanisms in compensated cardiac hypertrophy may play an adaptive role in maintaining heart function, whereas downregulation of this mechanism in decompensated cardiac hypertrophy may reflect the loss of its support to the failing heart. Although this study has identified differential changes in various components of the beta-adrenoceptor-mediated signal transduction system at compensated and decompensated stages of PO- and VO-induced cardiac hypertrophy, the mechanisms for such alterations remain to be investigated. Such studies may deal with gene and protein expression for different components of the beta-adrenoceptor signal transduction, as well as for the regulatory mechanisms, including G protein-coupled receptor kinases, beta-arrestins, and Gbeta{gamma} protein subunits. Since the renin-angiotensin and sympathetic nervous systems are activated on the induction of PO or VO, as well as during the development of congestive heart failure (11, 15, 16, 28, 29, 36, 37, 39), it is possible that the activation of these systems at the local level in the heart may upregulate the beta-adrenoceptor mechanisms during the compensated stages of cardiac hypertrophy, whereas their activation for prolonged periods may result in decompensated cardiac hypertrophy and downregulation of beta-adrenoceptor mechanisms. Similar mechanisms can be invoked with respect to an increase in ventricular wall stress to explain the biphasic changes in beta-adrenoceptor signal transduction during compensated and decompensated stages of cardiac hypertrophy, because PO or VO resulted in a progressive increase in the LVEDP. Since oxidative stress is increased during the development of heart failure (23) and oxidative stress has been shown to produce biphasic changes in the beta-adrenoceptor signal transduction (26), it is likely that the PO- or VO-induced differential alterations in beta-adrenoceptor mechanisms may also be the consequence of increased oxidative stress. Similar mechanisms have also been suggested to explain changes in beta-adrenoceptor signal transduction in left and right ventricles of infarcted animals (35).


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This research was supported by a grant from the Heart and Stroke Foundation of Manitoba. H. K. Saini is a predoctoral fellow of the Heart and Stroke Foundation of Canada.


   FOOTNOTES
 

Address for reprint requests and other correspondence: N. S. Dhalla, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Ave., Winnipeg, MB, Canada R2H 2A6 (e-mail: nsdhalla{at}sbrc.ca)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


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  1. Bohm M. Alterations of beta-adrenoceptor-G-protein-regulated adenylyl cyclase in heart failure. Mol Cell Biochem 147: 147–160, 1995.[CrossRef][ISI][Medline]
  2. Bristow MR, Feldman AM. Changes in the receptor-G protein-adenylyl cyclase system in heart failure from various types of heart muscle disease. Basic Res Cardiol 87: 15–35, 1992.
  3. Bristow MR, Hershberger RE, Port JD, Gilbert EM, Sandoval A, Rasmussen R, Cates AE, Feldman AM. beta-Adrenergic pathways in nonfailing and failing human ventricular myocardium. Circulation 82: I12–I25, 1990.
  4. Brodde OE. beta1- and beta2-adrenoceptors in the human heart: properties, function, and alterations in chronic heart failure. Pharmacol Rev 43: 203–242, 1991.[ISI][Medline]
  5. Brower GL, Janicki JS. Contribution of ventricular remodeling to pathogenesis of heart failure in rats. Am J Physiol Heart Circ Physiol 280: H674–H683, 2001.[Abstract/Free Full Text]
  6. Cantor EJ, Babick AP, Vasanji Z, Dhalla NS, Netticadan T. A comparative serial echocardiographic analysis of cardiac structure and function in rats subjected to pressure or volume overload. J Mol Cell Cardiol 38: 777–786, 2005.[CrossRef][ISI][Medline]
  7. Carabello BA, Zile MR, Tanaka R, Cooper G 4th. Left ventricular hypertrophy due to volume overload versus pressure overload. Am J Physiol Heart Circ Physiol 263: H1137–H1144, 1992.[Abstract/Free Full Text]
  8. Carabello BA. Concentric versus eccentric remodeling. J Card Fail 8: S258–S263, 2002.[CrossRef][ISI][Medline]
  9. Carabello BA. Models of volume overload hypertrophy. J Card Fail 2: 55–64, 1996.[CrossRef][Medline]
  10. Chakraborti S, Chakraborti T, Shaw G. beta-Adrenergic mechanisms in cardiac diseases: a perspective. Cell Signal 12: 499–513, 2000.[CrossRef][ISI][Medline]
  11. Dhalla NS, Golfman L, Liu X, Sasaki H, Elimban V, Rupp H. Subcellular remodeling and heart dysfunction in cardiac hypertrophy due to pressure overload. Ann NY Acad Sci 874: 100–110, 1999.[Abstract/Free Full Text]
  12. Dolgilevich SM, Siri FM, Atlas SA, Eng C. Changes in collagenase and collagen gene expression after induction of aortocaval fistula in rats. Am J Physiol Heart Circ Physiol 281: H207–H214, 2001.[Abstract/Free Full Text]
  13. Fan TH, Liang CS, Kawashima S, Banerjee SP. Alterations in cardiac beta-adrenoceptor responsiveness and adenylate cyclase system by congestive heart failure in dogs. Eur J Pharmacol 140: 123–132, 1987.[CrossRef][ISI][Medline]
  14. Frey N, Olson EN. Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol 65: 45–79, 2003.[CrossRef][ISI][Medline]
  15. Ganguly PK, Lee SL, Beamish RE, Dhalla NS. Altered sympathetic system and adrenoceptors during the development of cardiac hypertrophy. Am Heart J 118: 520–525, 1989.[CrossRef][ISI][Medline]
  16. Hannan RD, Jenkins A, Jenkins AK, Brandenburger Y. Cardiac hypertrophy: a matter of translation. Clin Exp Pharmacol Physiol 30: 517–527, 2003.[CrossRef][ISI][Medline]
  17. Homcy CJ, Vatner SF, Vatner DE. beta-Adrenergic receptor regulation in the heart in pathophysiologic states: abnormal adrenergic responsiveness in cardiac disease. Annu Rev Physiol 53: 137–159, 1991.[CrossRef][ISI][Medline]
  18. Karliner JS, Barnes P, Brown M, Dollery C. Chronic heart failure in the guinea pig increases cardiac {alpha}1- and beta-adrenoceptors. Eur J Pharmacol 67: 115–118, 1980.[CrossRef][ISI][Medline]
  19. Kaura D, Takeda N, Sethi R, Wang X, Nagano M, Dhalla NS. beta-Adrenoceptor mediated signal transduction in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters. Mol Cell Biochem 157: 191–196, 1996.[ISI][Medline]
  20. Litwin SE, Katz SE, Weinberg EO, Lorell BH, Aurigemma GP, Douglas PS. Serial echocardiographic-Doppler assessment of left ventricular geometry and function in rats with pressure-overload hypertrophy. Chronic angiotensin-converting enzyme inhibition attenuates the transition to heart failure. Circulation 91: 2642–2654, 1995.
  21. Mann DL, Spann JF, Cooper G. Basic mechanisms and models in cardiac hypertrophy: pathophysiological models. Mod Concepts Cardiovasc Dis 57: 7–11, 1988.
  22. Modesti PA, Vanni S, Bertolozzi I, Cecioni I, Polidori G, Paniccia R, Bandinelli B, Perna A, Liguori P, Boddi M, Galanti G, Serneri GG. Early sequence of cardiac adaptations and growth factor formation in pressure- and volume-overload hypertrophy. Am J Physiol Heart Circ Physiol 279: H976–H985, 2000.[Abstract/Free Full Text]
  23. Molavi B, Mehta JL. Oxidative stress in cardiovascular disease: molecular basis of its deleterious effects, its detection, and therapeutic considerations. Curr Opin Cardiol 19: 488–493, 2004.[CrossRef][ISI][Medline]
  24. Namba T, Tsutsui H, Tagawa H, Takahashi M, Saito K, Kozai T, Usui M, Imanaka-Yoshida K, Imaizumi T, Takeshita A. Regulation of fibrillar collagen gene expression and protein accumulation in volume-overloaded cardiac hypertrophy. Circulation 95: 2448–2454, 1997.
  25. Norton GR, Woodiwiss AJ, Gaasch WH, Mela T, Chung ES, Aurigemma GP, Meyer TE. Heart failure in pressure overload hypertrophy. The relative roles of ventricular remodeling and myocardial dysfunction. J Am Coll Cardiol 39: 664–671, 2002.[Abstract/Free Full Text]
  26. Persad S, Elimban V, Kaila J, Dhalla NS. Biphasic alterations in cardiac beta-adrenoceptor signal transduction mechanism due to oxyradicals. J Pharmacol Exp Ther 282: 1623–1631, 1997.[Abstract/Free Full Text]
  27. Plehn JF, Foster E, Grice WN, Huntington-Coats M, Apstein CS. Echocardiographic assessment of LV mass in rabbits: models of pressure and volume overload hypertrophy. Am J Physiol Heart Circ Physiol 265: H2066–H2072, 1993.[Abstract/Free Full Text]
  28. Post SR, Hammond HK, Insel PA. beta-Adrenergic receptors and receptor signaling in heart failure. Annu Rev Pharmacol Toxicol 39: 343–601, 1999.
  29. Ruzicka M, Keeley FW, Leenen FH. The renin-angiotensin system and volume overload-induced changes in cardiac collagen and elastin. Circulation 90: 1989–1996, 1994.
  30. Saini HK, Dhalla NS. Defective calcium handling in cardiomyocytes isolated from hearts subjected to ischemia-reperfusion. Am J Physiol Heart Circ Physiol 288: H2260–H2270, 2005.[Abstract/Free Full Text]
  31. Sethi R, Bector N, Takeda N, Nagano M, Jasmin G, Dhalla NS. Alterations in G-proteins in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters. Mol Cell Biochem 140: 163–170, 1994.[CrossRef][ISI][Medline]
  32. Sethi R, Dhalla KS, Beamish RE, Dhalla NS. Differential changes in left and right ventricular adenylyl cyclase activities in congestive heart failure. Am J Physiol Heart Circ Physiol 272: H884–H893, 1997.[Abstract/Free Full Text]
  33. Sethi R, Elimban V, Chapman D, Dixon IM, Dhalla NS. Differential alterations in left and right ventricular G-proteins in congestive heart failure due to myocardial infarction. J Mol Cell Cardiol 30: 2153–2163, 1998.[CrossRef][ISI][Medline]
  34. Sethi R, Panagia V, Dhalla KS, Beamish RE, Jasmine G, Dhalla NS. Status of beta-adrenergic mechanisms during the development of congestive heart failure in cardiomyopathic hamsters (UM-X7.1). In: The Cardiomyopathic Heart, edited by Nagano M, Takeda N, and Dhalla NS. New York: Raven, 1994, p. 73–86.
  35. Sethi R, Saini HK, Wang X, Elimban V, Babick A, Dhalla NS. Differential changes in beta-adrenoceptor signal transduction in left and right ventricles of infarcted rats. Can J Physiol Pharmacol 84: 747–754, 2006.[CrossRef][ISI][Medline]
  36. Sethi R, Shao Q, Ren B, Saini HK, Takeda N, Dhalla NS. Changes in beta-adrenoceptors in heart failure due to myocardial infarction are attenuated by blockade of renin-angiotensin system. Mol Cell Biochem 263: 11–20, 2004.[CrossRef][ISI][Medline]
  37. Sethi R, Shao Q, Takeda N, Dhalla NS. Attenuation of changes in Gi-proteins and adenylyl cyclase in heart failure by an ACE inhibitor, imidapril. J Cell Mol Med 7: 277–286, 2003.[ISI][Medline]
  38. Stiles GL, Caron MG, Lefkowitz RJ. beta-Adrenergic receptors: biochemical mechanisms of physiological regulation. Physiol Rev 64: 661–743, 1984.[Free Full Text]
  39. Vatner DE, Asai K, Iwase M, Ishikawa Y, Shannon RP, Homcy CJ, Vatner SF. beta-Adrenergic receptor-G protein-adenylyl cyclase signal transduction in the failing heart. Am J Cardiol 83: 80H–85H, 1999.[CrossRef][ISI][Medline]
  40. Vatner DE, Homcy CJ, Sit SP, Manders WT, Vatner SF. Effects of pressure overload, left ventricular hypertrophy on beta-adrenergic receptors, and responsiveness to catecholamines. J Clin Invest 73: 1473–1482, 1984.[ISI][Medline]
  41. Vatner DE, Vatner SF, Fujii AM, Homcy CJ. Loss of high affinity cardiac beta-adrenergic receptors in dogs with heart failure. J Clin Invest 76: 2259–2264, 1985.[ISI][Medline]
  42. Wang X, Ren B, Liu S, Sentex E, Tappia PS, Dhalla NS. Characterization of cardiac hypertrophy and heart failure due to volume overload in the rat. J Appl Physiol 94: 752–763, 2003.[Abstract/Free Full Text]
  43. Wang X, Sentex E, Chapman D, Dhalla NS. Alterations of adenylyl cyclase and G proteins in aortocaval shunt-induced heart failure. Am J Physiol Heart Circ Physiol 287: H118–H125, 2004.[Abstract/Free Full Text]
  44. Wang X, Sentex E, Saini HK, Chapman D, Dhalla NS. Upregulation of beta-adrenergic receptors in heart failure due to volume overload. Am J Physiol Heart Circ Physiol 289: H151–H159, 2005.[Abstract/Free Full Text]
  45. Wikman-Coffelt J, Parmley WW, Mason DT. The cardiac hypertrophy process. Analyses of factors determining pathological vs. physiological development. Circ Res 45: 697–707, 1979.[Free Full Text]




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