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J Appl Physiol 84: 884-889, 1998;
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Vol. 84, Issue 3, 884-889, March 1998

Vasoconstrictor responses of coronary resistance arteries in exercise-trained pigs

M. Harold Laughlin and Judy M. Muller

Departments of Veterinary Biomedical Sciences and Medical Physiology, The Dalton Cardiovascular Research Center, and Division of Cardiology, College of Medicine, University of Missouri, Columbia, Missouri 65211

    ABSTRACT
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

Coronary resistance arteries isolated from exercise-trained pigs have been shown to exhibit enhanced myogenic reactivity (J. M. Muller, P. R. Myers, and M. Harold Laughlin. J. Appl. Physiol. 75: 2677-2682, 1993). The purpose of this study was to test the hypothesis that exercise training results in enhanced vasoconstrictor responses of these arteries to all vasoconstrictor stimuli [specifically acetylcholine (ACh), endothelin-1 (ET-1), KCl, and the Ca2+ channel-agonist Bay K 8644]. Female Yucatan miniature swine were trained (Trn) on a motor-driven treadmill (n = 16) or remained sedentary (Sed, n = 15) for 16-20 wk. Arteries 50-120 µm in diameter were isolated and cannulated with micropipettes, and intraluminal pressure was set at 60 cmH2O throughout experiments. Vasoreactivity was evaluated by examining constrictor responses to increasing concentrations of ACh (10-9 to 10-4 M), ET-1 (10-10 to 10-8 M), KCl (bath replacement with isotonic physiological saline solution containing 30 or 80 mM), and Bay K 8644 (10-9 to 10-6 M). Constricted diameters are expressed relative to the passive diameter observed after 100 µM SNP. All four constrictors produced similar decreases in diameter in arteries from both groups [ACh: 0.52 ± 0.07 (Trn) and 0.54 ± 0,06 (Sed); ET-1: 0.66 ± 0.05 (Trn) and 0.70 ± 0.07 (Sed); KCl: 0.66 ± 0.05 (Trn) and 0.70 ± 0.07 (Sed); Bay K 8644: 0.86 ± 0.05 (Trn) and 0.76 ± 0.05 (Sed)]. Present results combined with previous observations indicate that exercise training does not alter vasoconstrictor responses of porcine coronary resistance arteries but specifically increases myogenic reactivity. Thus the underlying cellular mechanisms for myogenic tone are altered by training but not receptor-mediated mechanisms (ACh and ET-1) nor voltage-gated Ca2+ channels (KCl and Bay K 8644) in coronary resistance arteries.

albumin; spontaneous tone; vascular smooth muscle; acetylcholine; endothelin; Bay K 8644; nitroprusside

    INTRODUCTION
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

CORONARY BLOOD FLOW and capillary exchange capacities are increased in the hearts of exercise-trained pigs (17, 23). The increased transport capacity of the coronary circulation is associated with changes in local control of coronary resistance (17, 23) and vasoreactivity of coronary arteries (21, 22) and the control of intracellular calcium by the sarcoplasmic reticulum in coronary vascular smooth muscle (25, 26). The myogenic response, the ability of blood vessels to constrict in response to elevations in intraluminal pressure and dilate when intraluminal pressure decreases, appears to be an intrinsic property of resistance arteries and is believed to be critically important in control of vascular resistance in the microcirculation (3, 5, 6, 9, 13, 18). Coronary resistance arteries isolated from exercise-trained (Trn) pigs exhibit increased myogenic reactivity (20). Specifically, comparison of pressure-diameter curves of isolated, cannulated arteries revealed that arteries from Trn pigs constrict more than arteries from control pigs as intraluminal pressure was raised to and above 60 mmHg. The mechanisms responsible for the enhanced myogenic reactivity in coronary resistance arteries have not been determined.

DiCarlo et al. (4) reported that exercise training in dogs produced enhanced sensitivity of coronary resistance arteries to norepinephrine. The results of this study (4), considered together with those by Muller et al. (20), suggest the hypothesis that exercise training produces increased sensitivity of coronary resistance arteries to all vasoconstrictor stimuli, including the response to stretch (myogenic response). Thus increased myogenic reactivity after exercise training may reflect a generalized enhancement of all vasoconstrictor responses in coronary resistance arteries. The purpose of this study was to test this hypothesis. Responses of coronary resistance arteries to receptor-mediated and voltage-gated calcium channel-mediated vasoconstrictions were examined in coronary resistance arteries isolated from exercise trained and sedentary pigs. An in vitro, isolated artery preparation was used to determine vasoconstrictor responses, independent of confounding neural or humoral influences, that might be found in the intact heart.

    MATERIALS AND METHODS
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

Experimental animals. Adult female miniature swine weighing 25-40 kg were obtained from the breeder (Charles River) and randomly divided into groups of Trn pigs and sedentary control (Sed) pigs. The Trn pigs were placed on the same progressive treadmill training program used by Muller et al. (20), which is a modification of the program designed by Tipton et al. (27). Sed pigs were confined to their pens during the training period (16-20 wk). This is the same training program our laboratory has used for miniature swine in previous studies (17, 20-23, 25, 26).

Training program. All animals used in this study were housed and maintained in accordance with standards set forth by the American Association for Laboratory Animal Care and the University of Missouri Institutional Animal Care and Use Committee. In week 1 of training, Trn pigs walked on the treadmill for 5 min at 2.5 mph to warm-up. After the warm-up, the pigs ran on the treadmill at 5 miles/h (mph) for 15 min (sprint) and at 3 mph for 20-30 min (endurance). Pigs were fed after treadmill training bouts as positive reinforcement of the behavior (17, 19, 21-23). The intensity and duration of exercise bouts increased steadily so that by the week 12 of training the pigs ran 85 min/day, 5 days/wk. At this time, the 85-min training bouts consisted of a 5-min warm-up at a speed of 2.5 mph, a 15-min sprint run at speeds of 6-8 mph, a 60-min endurance run at speeds of 4-6 mph, and a 5-min warm-down at a speed of 2 mph. Actual running speeds during the sprint and endurance runs depended on the ability of each pig to perform on the treadmill.

Treadmill performance test. At the beginning and again at the end of the training period, treadmill performance tests were administered to both Trn and Sed pigs to evaluate exercise tolerance. The treadmill performance test consisted of four stages of exercise (17). In stage 1 the pigs ran 3.1 mph with 0% grade for 5 min. In stage 2 the pigs continued to run at 3.1 mph for 10 min, and the grade was increased to 10%. In stage 3 speed was increased to 4.3 mph, whereas the grade remained at 10%. The pigs ran for 10 min in this stage. In the final stage (stage 4) the pigs ran up a 10% grade at 6 mph until exhaustion. A three-lead electrocardiogram was used to measure heart rates continuously throughout the test. Total exercise times were also recorded.

Oxidative enzyme capacity. Samples were taken from the middle of the triceps brachii muscles, frozen, and stored at -70°C until processed. Citrate synthase activity was measured in the samples by using the spectrophotometric assay described by Srere (24).

Preparation of coronary resistance arteries. After completion of exercise training (or sedentary confinement), pigs were sedated with ketamine (30 mg/kg) and anesthetized with pentobarbital sodium (30 mg/kg). The hearts were rapidly removed and placed in cold physiological saline solution (PSS; 4°C). The weight of the heart was recorded, and a portion of the left ventricular wall was isolated and placed in a dissection chamber containing cold PSS. Resistance arteries 50-120 µm in intraluminal diameter and ~1 mm in length were isolated from the surrounding tissue 0.5-3.0 mm below the epicardial surface with the aid of a dissecting microscope. Resistance arteries were placed in a Plexiglas chamber containing PSS-albumin solution equilibrated with room air at ambient temperature. Each end of the vessel was cannulated with a glass micropipette (~50 µm diameter and filled with filtered PSS-albumin) and secured with 11-0 ophthalmic suture. The vessel was stretched to the length measured before removal from the myocardium. The glass micropipettes were connected to independent reservoirs, and intraluminal pressure was set at 60 cmH2O, with zero intraluminal flow, by raising the reservoirs 60 cm above the vessel chamber. Pressures were measured through side arms of the two reservoirs with low-volume displacement transducers (model BP100 transducer, AD Instruments). If the arteries would not maintain pressure (due to leaks), they were removed from the chamber and discarded. The cannulated vessel was viewed through an inverted microscope (Nikon Diaphot TMD) with a ×20-40 lens, numerical aperture of 0.4 (ELWD). The microscope was coupled to a video camera (Panasonic WV 1,500x) and TV monitor (Panasonic TR930B). An image of the vessel was displayed on the TV monitor, and intraluminal diameter measurements were made continuously by using a video tracking device (Texas A & M) as described previously (12, 13, 20, 21). The tracking system was calibrated with a stage micrometer showing 10-µm divisions. The resolution of the system allowed measurement of changes in vessel diameter as small as 2 µm. The tracking device produced a direct current signal that was recorded on a computer data-acquisition system (MacLab) at a sampling rate of 4 samples/s.

The PSS used in these experiments consisted of (in mM) 145 NaCl, 4.7 KCl, 2.0 CaCl2, 1.17 MgSO4, 1.2 NaH2PO4, 5.0 glucose, 2.0 pyruvate, 0.02 EDTA, and 3.0 3-(N-morpholino)-propanesulfonic acid buffer. The PSS pH was adjusted to 7.4 and filtered through 0.22-µm filters (Fisher Scientific, Pittsburgh, PA). All drugs were obtained from Sigma Chemical (St. Louis, MO) unless otherwise specified. Drugs were dissolved in PSS-albumin and administered to the bath surrounding the artery. PSS-albumin contained 10 mg/ml bovine serum albumin (bovine, fraction V: 98-99% albumin, US Biochemical) as described previously (7, 13, 19, 20).

Experimental procedure. Vessels were allowed to equilibrate at an intraluminal pressure of 60 cmH2O for 1 h, during which time the temperature of the chamber was raised to and maintained at 37 ± 1°C with a circulating water bath. During the 1-h equilibration period, the PSS-albumin was replaced three times with fresh PSS-albumin (37°C).

Sensitivity to receptor-mediated vasoconstrictor agonists was evaluated by examining responses to acetylcholine (ACh) and endothelin-1 (ET-1), direct vascular smooth muscle vasoconstrictor agents in pig coronary arteries. These vasoconstrictor agonists were selected because they are receptor-mediated constrictors that preliminary experiments revealed consistently produced vasoconstriction. Concentration-response curves were obtained by cumulative additions of small aliquots of concentrated stock solution directly into the bath; drug concentrations (10-9 to 10-4 M ACh; 10-10 to 10-8 M ET-1) were increased after the response to the preceding dose was maximal. To examine contractions mediated by voltage-gated calcium channels, responses to KCl and Bay K 8644 were examined. Concentration-response curves were obtained by cumulative additions of small aliquots of concentrated stock solution directly into the bath; drug concentrations (5 to 100 mM KCl; 10-9 to 10-6 M Bay K 8644) were increased after the response to the preceding dose was maximal. Arteries that did not respond (20% constriction) to KCl and ACh or ET-1 were deleted from the study. Spontaneous tone was not used as a selection criterion in this study. Arteries that developed spontaneous tone (15% constriction) were generally used for other protocols. Some arteries did not constrict in response to addition of KCl to the bath. To determine whether this lack of responsiveness was due to the cumulative addition of KCl to the bath, responses to bath replacement with isotonic PSS containing 30 or 80 mM KCl were examined in arteries from eight Sed and eight Trn pigs.

Finally, at the end of each experiment, each artery was exposed to 100 µM sodium nitroprusside (SNP) in PSS-albumin solution to determine maximal diameter at 60 cmH2O intraluminal pressure. Diameters were normalized to this measurement as described previously by Kuo et al. (9, 12, 13) and Muller et al. (20). This pressure, 60 cmH2O, was selected because in vivo microvascular pressure measurements obtained by Chilian et al. (2) in the beating cat ventricle indicate that intravascular pressure in vessels of this size is ~60 cmH2O.

Data analysis. Vasomotor responses are presented as absolute diameters and as normalized diameters. The diameter measured at 60 cmH2O intraluminal pressure in the presence of 100 µM SNP was defined as the reference diameter and was assigned a value of 1.0. All normalized diameter measurements are expressed relative to this diameter, as described by Kuo et al. (9, 10, 11, 13). Responses were compared between Trn and Sed groups by analysis of variance (ANOVA) for repeated measures. Diameters measured at each dose were compared between Trn and Sed groups with ANOVA for repeated measures by using SuperANOVA software. No post hoc tests were employed because ANOVA did not indicate that differences existed between groups. Significance of differences between mean values for treadmill performance times, citrate synthase activity, and heart weight-to-body weight ratio were determined by an unpaired t-test. In all statistical analyses, n is the number of pigs. Significance was defined as P < 0.05.

    RESULTS
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Abstract
Introduction
Materials & Methods
Results
Discussion
References

Physiological state of animals. As expected, the training program resulted in significant increases in the endurance of the Trn pigs (17, 20-23, 25, 26). Thus, by week 16 of training, Trn pigs were able to complete 85-min running bouts on the treadmill whereas during the first week of training fatigue generally occurred after 30-40 min of treadmill exercise. Further indication of the effectiveness of training are given in Table 1. Heart weight, heart weight-to-body weight ratio, and citrate synthase activity of skeletal muscles were significantly higher in the Trn pigs. Trn pigs also had significantly longer running times during performance testing. Heart rates were significantly lower in Trn pigs during all stages of treadmill performance testing (Table 1).

                              
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  		Table 1.   Characteristics of animals and treadmill performance test heart rate data

Characteristics of isolated coronary resistance arteries. Mean intraluminal diameter measured at 60 cmH2O in the presence of 100 µM SNP was similar in resistance arteries isolated from Trn (115 ± 5 µm) and Sed (109 ± 5 µm) pigs. The range of passive intraluminal diameter was from 73 to 221 µm and from 67 to 202 µm in vessels from Trn and Sed pigs, respectively.

Only vessels that constricted at least 20% to vasoconstrictor agents were included in data analysis. In keeping with this selection criterion, no response to vasoconstrictor agents was observed in 4 of 43 vessels from Trn pigs and in 2 of 45 arteries from Sed pigs.

During the initial equilibration period at 60 cmH2O, most vessels from Trn and Sed pigs developed similar spontaneous tone. In the Trn group the mean normalized diameter after equilibration was 0.93 ± 0.01 µm, and in the Sed group the diameter was 0.94 ± 0.01 µm. Spontaneous tone, >= 5% of normalized diameter, was present in 22 of 39 arteries from Trn pigs and in 18 of 43 arteries from Sed pigs. Thus the incidence of spontaneous tone and of nonresponsive arteries was similar in vessels from Trn and Sed pigs. It should be noted that in a previous study from our laboratory (20), which focused on myogenic responsiveness, arteries were selected that constricted >= 15% in response to increasing intraluminal pressure. This selection criterion was not used in the present study.

Responses to receptor-mediated vasoconstrictor agents. ACh produced dose-dependent constriction in arteries from both groups (Fig. 1). ACh sensitivity and maximal ACh-induced contraction of arteries isolated from Trn and Sed pigs were similar. ET-1 also produced dose-dependent constriction in arteries from both groups, and sensitivity and maximal ET-1-induced contraction were also similar (Fig. 2). ET-1 is a more potent vasoconstrictor agent than ACh, as reflected by the fact that constriction was apparent at doses of 10-10 M ET-1. Doses of ET-1 greater than 10-9 M generally caused complete constriction.


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  		Fig. 1.   Vasoconstrictor responses to increasing doses of acetylcholine in coronary resistance arteries from sedentary (Sed) and exercise-trained (Trn) pigs. Diameters were normalized to diameter measured in response to 100 µM nitroprusside at 60 cmH2O. Values are means ± SE. n, No. of animals.


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  		Fig. 2.   Vasoconstrictor responses to increasing doses of endothelin in coronary resistance arteries from Sed and Trn pigs. Diameters were normalized to diameter measured in response to 100 µM nitroprusside at 60 cmH2O. Values are means ± SE.

Cumulative addition of KCl generally produced dose-dependent constriction in arteries from both groups (data not shown). However, KCl occasionally produced no response or even vasodilation in some vessels. To determine whether these results were influenced by the hypertonic conditions produced by cumulative addition of KCl to the bath, we conducted a series of experiments in which the bath was replaced with isotonic PSS containing 30 or 80 mM KCl. The results of this experiment are shown in Fig. 3. In both Trn and Sed groups, replacement of PSS produced greater constriction with both 30 and 80 mM KCl than did cumulative addition of KCl. These results indicate that the response of coronary resistance arteries to changes in membrane potential produced by KCl is similar in Trn and Sed animals. Finally, Bay K 8644, a selective L-type calcium channel-agonist, produced dose-dependent constriction in arteries from both groups (Fig. 4).


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  		Fig. 3.   Vasoconstrictor responses to 30 and 80 mM KCl in coronary resistance arteries from Sed and Trn pigs. Diameters were normalized to diameter measured in response to 100 µM nitroprusside at 60 cmH2O. Values are means ± SE; n = 8 Sed and 8 Trn animals. rep, Replacement of bath with isotonic PSS-albumin (PSSA) containing 30 or 80 mM KCl; add, cumulative addition of KCl.


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  		Fig. 4.   Vasoconstrictor responses to increasing doses of Bay K 8644 (M) in coronary resistance arteries from Sed and Trn pigs. Values are means ± SE. Results are expressed as absolute diameters (A), and diameter relative to initial diameter was determined in presence of 30 mM KCl (B). PSSA contained 30 mM KCl.

    DISCUSSION
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

The purpose of this study was to test the hypothesis that exercise training results in enhanced vasoconstrictor responses of coronary resistance arteries to all vasoconstrictor stimuli (specifically, ACh, ET-1, KCl, and the calcium channel-agonist Bay K 8644 were examined). An in vitro approach was used to evaluate the effects of exercise training on contractile responses of coronary resistance arteries to ACh and ET-1, agents that induce contraction via receptor-mediated mechanisms, and to two agents that induce contraction via opening of voltage-gated calcium channels in the vascular smooth muscle sarcolemma, KCl and Bay K 8644. The results indicate that vasoconstrictor responses signaled by receptor-mediated mechanisms (ACh and ET-1) and by voltage-gated calcium channels (KCl and Bay K 8644) were similar in coronary resistance arteries isolated from Sed and Trn pigs. These results, combined with the previously observed increase in the myogenic response in coronary resistance arteries isolated from exercise-trained pigs (20), suggest that exercise training specifically increases myogenic reactivity. It is important that the pigs in the present study were trained by using a training program identical to that of Muller et al. (20). Present results also indicate that the underlying cellular mechanisms responsible for the enhanced myogenic reactivity do not involve the L-type calcium channels in the sarcolemma or receptor-second messenger signaling systems used by ACh or ET-1 in vascular smooth muscle cells in coronary resistance arteries.

The hypothesis for this study was based on results from previous studies that indicate that exercise training alters coronary vasomotor control at the whole organ and/or microvascular level (1, 4, 14-17, 20-23, 25, 26). Results from the intact coronary circulation indicate that reactivity of coronary resistance arteries to vasodilator stimuli (4, 14, 15, 17, 23) and vasoconstrictor stimuli (4) is increased after exercise training. DiCarlo et al. (4) reported that the norepinephrine-induced vasoconstrictor responses of coronary resistance arteries in conscious dogs were increased after exercise training. The cause of the difference between results of the present study and those of DiCarlo et al. (4) cannot be established at this time. However, we do not believe the differing results necessarily indicate that vascular adaptations to exercise training are different in the coronary circulation of dogs and pigs. Rather, in vivo measurements of coronary function reflect an average response of all sizes of coronary resistance arteries throughout the coronary arterial tree. Because vasomotor responsiveness is not uniform throughout the coronary arterial tree, regional changes in vasomotor function may be masked by compensatory responses at other levels in the arterial tree (11). For example, constriction of large resistance arteries may produce metabolic vasodilation of small resistance arteries so that total vascular resistance measured across the entire vascular tree is not different, whereas changes occurred regionally along the arterial tree (8). It is also possible that the observations of DiCarlo et al. (4) are norepinephrine specific, which cannot be tested in isolated coronary resistance arteries. Other neural-humoral factors present in vivo could also be responsible for the increased sensitivity to norepinephrine in trained dogs rather than the sensitivity of vascular smooth muscle in coronary resistance arteries to vasoconstrictor agents.

Muller et al. (20) reported that myogenic constriction in response to increased intraluminal pressure was enhanced in coronary resistance arteries from exercise-trained pigs. Kuo et al. (9, 10) reported that myogenic responses of porcine coronary resistance arteries are endothelium independent. Therefore, the enhanced myogenic reactivity reported by Muller et al. (20) likely results from a change in the vascular smooth muscle in these arteries. These results combined with present observations suggest that this effect of exercise training on coronary resistance arteries is somehow specific to contractions induced by stretch.

Exercise training has been shown to increase the reactivity of the coronary microcirculation to vasodilator stimuli (4, 14, 15, 17, 23) and vasoconstrictor stimuli (4). We selected the resistance artery size used in the present study because the bulk of vascular resistance in the coronary circulation lies in arteries in this size range (8, 11). Present results indicate that training does not alter responses of coronary resistance arteries to vasoconstrictor agents (Figs. 1-4). This lack of effect of training on vascular smooth muscle in these arteries is consistent with a lack of effect of training on direct vascular smooth muscle vasodilator responses of this size of coronary resistance arteries (21). Muller et al. (21) reported that endothelium-dependent vasodilation is enhanced after training. Present results combined with these previous results indicate that the only direct vascular smooth muscle vasomotor response of coronary resistance arteries that is altered by exercise training is myogenic reactivity (20). Presently, available data do not allow us to determine the significance of these changes to the control of coronary blood flow. Even in the absence of a change in total coronary blood flow per se, it is possible that the enhancement of these two opposing control mechanisms in the coronary microcirculation results in improved control of myocardial perfusion (8, 10, 11).

    ACKNOWLEDGEMENTS

The authors thank Miles A. Tanner, Pam Thorne, Tammy Knox, Tammy Strawn, and Denise Stowers for important technical contributions to this work.

    FOOTNOTES

This work was supported by National Heart, Lung, and Blood Institute Grant HL-52490.

Address for reprint requests: M. Laughlin, E102 Veterinary Medical Bldg., Univ. of Missouri, Columbia, MO 65211.

Received 28 July 1997; accepted in final form 12 November 1997.

    REFERENCES
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

1.   Bove, A. A., and J. D. Dewey. Proximal coronary vasomotor reactivity after exercise training in dogs. Circulation 71: 620-625, 1985[Medline].

2.   Chilian, W. M., C. L. Eastham, and M. L. Marcus. Microvascular distribution of coronary vascular resistance in beating left ventricle. Am. J. Physiol. 251 (Heart Circ. Physiol. 20): H779-H788, 1986[Abstract/Free Full Text].

3.   D'Angelo, G., and G. A. Meininger. Transduction mechanisms involved in the regulation of myogenic activity. Hypertension 23: 1096-1105, 1994[Abstract].

4.   DiCarlo, S. E., R. W. Blair, V. S. Bishop, and H. L. Stone. Daily exercise enhances coronary resistance vessel sensitivity to pharmacological activation. J. Appl. Physiol. 66: 421-428, 1989[Abstract/Free Full Text].

5.   Halpern, W., G. Osol, and G. Coy. Mechanical behavior of pressurized in vitro prearteriolar vessels determined with a video system. Ann. Biomed. Eng. 12: 463-479, 1984[Medline].

6.   Harder, D. Pressure-induced myogenic activation of cat cerebral arteries is dependent on intact endothelium. Circ. Res. 60: 102-107, 1987[Abstract].

7.   Jackson, P. A., and B. R. Duling. Myogenic response and wall mechanics of arterioles. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1147-H1155, 1989[Abstract/Free Full Text].

8.   Jones, C. J. H., L. Kuo, M. J. Davis, D. V. Defily, and W. M. Chilian. Role of nitric oxide in the coronary microvascular responses to adenosine and increased metabolic demand. Circulation 91: 1807-1813, 1995[Medline].

9.   Kuo, L., W. M. Chilian, and M. J. Davis. Coronary arteriolar myogenic response is independent of endothelium. Circ. Res. 66: 860-866, 1990[Abstract].

10.   Kuo, L., W. M. Chilian, and M. J. Davis. Interaction of pressure- and flow-induced responses in porcine coronary resistance vessels. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H1706-H1715, 1991[Abstract/Free Full Text].

11.   Kuo, L., W. M. Chilian, and M. J. Davis. Longitudinal gradients for endothelium-dependent and -independent vascular responses in the coronary microcirculation. Circulation 92: 518-525, 1995[Medline].

12.   Kuo, L., W. M. Chilian, M. J. Davis, and M. H. Laughlin. Endotoxin impairs flow-induced vasodilation of porcine coronary arterioles. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H1838-H1845, 1992[Abstract/Free Full Text].

13.   Kuo, L., M. J. Davis, and W. M. Chilian. Myogenic activity in isolated subepicardial and subendocardial coronary arterioles. Am. J. Physiol. 255 (Heart Circ. Physiol. 24): H1558-H1562, 1988[Abstract/Free Full Text].

14.   Laughlin, M. H. Effects of exercise training on coronary transport capacity. J. Appl. Physiol. 58: 468-476, 1985[Abstract/Free Full Text].

15.   Laughlin, M. H., J. N. Diana, and C. M. Tipton. Effects of chronic exercise training on coronary reactive hyperemia and coronary blood flow in the dog. J. Appl. Physiol. 45: 604-610, 1978[Abstract/Free Full Text].

16.   Laughlin, M. H., and R. M. McAllister. Exercise training-induced coronary vascular adaptation. J. Appl. Physiol. 73: 2209-2225, 1992[Abstract/Free Full Text].

17.   Laughlin, M. H., K. A. Overholser, and M. J. Bhatte. Exercise training increases coronary transport reserve in miniature swine. J. Appl. Physiol. 67: 1140-1149, 1989[Abstract/Free Full Text].

18.   Meininger, G. A., and M. J. Davis. Cellular mechanisms involved in the vascular myogenic response. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H647-H659, 1992[Abstract/Free Full Text].

19.   Muller, J. M., M. H. Laughlin, and P. R. Myers. Vasoactivity of isolated coronary microvessels: influence of albumin. Microvasc. Res. 46: 107-115, 1993[Medline].

20.   Muller, J. M., P. R. Myers, and M. H. Laughlin. Exercise training alters myogenic responses in porcine coronary resistance arteries. J. Appl. Physiol. 75: 2677-2682, 1993[Abstract/Free Full Text].

21.   Muller, J. M., P. R. Myers, and M. H. Laughlin. Vasodilator responses of coronary resistance arteries from exercise trained pigs. Circulation 89: 2308-2314, 1994[Medline].

22.   Oltman, C. L., J. L. Parker, H. R. Adams, and M. H. Laughlin. Effects of exercise training on vasomotor reactivity of porcine coronary arteries. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H372-H382, 1992[Abstract/Free Full Text].

23.   Overholser, K. A., M. H. Laughlin, and M. J. Bhatte. Exercise training-induced increase in coronary transport capacity. Med. Sci. Sports Exerc. 26: 1239-1244, 1994[Medline].

24.   Srere, P. A. Citrate synthase. Methods Enzymol. 13: 3-5, 1969.

25.   Stehno-Bittel, L., M. H. Laughlin, and M. Sturek. Exercise training alters calcium release from coronary smooth muscle sarcoplasmic reticulum. Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H643-H647, 1990[Abstract/Free Full Text].

26.   Stehno-Bittel, L., M. H. Laughlin, and M. Sturek. Exercise training depletes sarcoplasmic reticulum calcium in coronary smooth muscle. J. Appl. Physiol. 71: 1764-1773, 1991[Abstract/Free Full Text].

27.   Tipton, C. M., R. A. Carey, W. C. Eastin, and H. H. Erickson. A submaximal test for dogs: evaluation of the effects of exercise training, detraining, and cage confinement. J. Appl. Physiol. 37: 271-275, 1974[Free Full Text].

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M. H. Laughlin, L. J. Rubin, J. W. E. Rush, E. M. Price, W. G. Schrage, and C. R. Woodman
Short-term training enhances endothelium-dependent dilation of coronary arteries, not arterioles
J Appl Physiol, January 1, 2003; 94(1): 234 - 244.
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 J. Appl. Physiol.Home page
C. L. Heaps and D. K. Bowles
Gender-specific K+-channel contribution to adenosine-induced relaxation in coronary arterioles
J Appl Physiol, February 1, 2002; 92(2): 550 - 558.
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 J. Appl. Physiol.Home page
M. H. Laughlin, J. S. Pollock, J. F. Amann, M. L. Hollis, C. R. Woodman, and E. M. Price
Training induces nonuniform increases in eNOS content along the coronary arterial tree
J Appl Physiol, February 1, 2001; 90(2): 501 - 510.
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 J. Appl. Physiol.Home page
M. H. Laughlin, W. G. Schrage, R. M. McAllister, H. A. Garverick, and A. W. Jones
Interaction of gender and exercise training: vasomotor reactivity of porcine skeletal muscle arteries
J Appl Physiol, January 1, 2001; 90(1): 216 - 227.
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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
R. E. Gandley, K. P. Conrad, and M. K. McLaughlin
Endothelin and nitric oxide mediate reduced myogenic reactivity of small renal arteries from pregnant rats
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2001; 280(1): R1 - R7.
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