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Department of Pediatrics, Harbor-UCLA Medical Center, University of California, Los Angeles, School of Medicine, Torrance, California 90509
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ABSTRACT |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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-Adrenergic agonists are important regulators
of perinatal pulmonary circulation. They cause vasodilation primarily
via the adenyl cyclase-adenosine 3',5'-cyclic monophosphate
(cAMP) pathway. We examined the responses of isolated fourth-generation
pulmonary veins of term fetal (145 ± 2 days gestation)
and newborn (10 ± 1 days) lambs to isoproterenol, a -adrenergic
agonist. In vessels preconstricted with U-46619 (a thromboxane
A2 analog), isoproterenol induced
greater relaxation in pulmonary veins of newborn lambs than in those of
fetal lambs. The relaxation was eliminated by propranolol, a
-adrenergic antagonist. Forskolin, an activator of adenyl cyclase,
also caused greater relaxation of veins of newborn than those of fetal
lambs. 8-Bromoadenosine 3',5'-cyclic monophosphate, a cell
membrane-permeable analog of cAMP, induced a similar relaxation of all
vessels. Biochemical studies show that isoproterenol and forskolin
induced a greater increase in cAMP content and in adenyl cyclase
activity of pulmonary veins in the newborn than in the fetal lamb.
These results demonstrate that -adrenergic-agonist-mediated
relaxation of pulmonary veins increases with maturation. An increase in
the activity of adenyl cyclase may contribute to the change.
-adrenergic agonist; adenyl cyclase; vascular smooth muscle; neonatal pulmonary circulation
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INTRODUCTION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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AT BIRTH, pulmonary vascular resistance decreases >10-fold and pulmonary blood flow increases 8- to 10-fold. These marked changes are necessary for the lungs to replace the placenta for gaseous exchange (7, 25). Pulmonary vascular resistance is determined by the reactivity of arteries, capillaries, and veins (22). However, little is known about the developmental change in venous vasomotor activity.
In lambs, under basal conditions, pulmonary veins contribute ~36% of total pulmonary vascular resistance (22); when stimulated with thromboxane, platelet-activating factor, endothelin, and hypoxia, pulmonary veins constrict as vigorously as or even more than arteries (21, 23, 24). The activity of pulmonary veins is developmentally regulated (28). For instance, relaxation of pulmonary veins mediated by endothelium-derived nitric oxide is markedly greater in newborn lambs than in term fetal lambs (9, 10, 28).
-Adrenoceptor agonists are important modulators of perinatal
pulmonary vasoactivity (1). They cause vasodilation by activating adenyl cyclase followed by an increase in the intracellular adenosine 3',5'-cyclic monophosphate (cAMP) content and vasodilation
(1, 19). In the present study, by measuring the vessel tension, intracellular cAMP content, and adenyl cyclase activity, we determined whether there is a developmental change in -adrenoceptor-mediated response of pulmonary veins of perinatal lambs.
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MATERIALS AND METHODS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Fifteen term fetal lambs (143-149 days gestation, term being 150 days gestation; either sex) from 7 pregnant ewes and 13 newborn lambs (8-13 days old, either sex) from Nebeker Ranch (Lancaster, CA) were used. After an overnight fast, the ewe was anesthetized with ketamine hydrochloride (30 mg/kg im). Then, the fetus was delivered by cesarean section and killed by a lethal dose of pentobarbital sodium (100 mg/kg iv) via the umbilical vein. The ewe was killed with an overdose of pentobarbital sodium. Newborn lambs were anesthetized with ketamine hydrochloride (30 mg/kg im) and then killed with an overdose of pentobarbital sodium.
The lungs were immediately removed, and fourth-generation pulmonary veins (OD: 1.5-2.5 mm) were dissected free of parenchyma and cut into rings (length: 3 mm).
Organ chamber study. Vessel rings were suspended in organ chambers filled with 10 ml of modified Krebs-Ringer bicarbonate solution [composition (in mM): 118.3 NaCl, 4.7 KCl, 2.5 CaCl2, 1.2 MgSO4, 1.2; KH2PO4, 25.0 NaHCO3, 11.1 glucose] maintained at 37 ± 0.5°C and aerated with 95% O2-5% CO2 (pH = 7.4). Each ring was suspended by two stirrups passed through the lumen. One stirrup was anchored to the bottom of the organ chamber; the other one was connected to a strain gauge (model FT03C, Grass Instruments, Quincy, MA) for the measurement of isometric force (10).
At the beginning of the experiment, each vessel ring was stretched to its optimal resting tension. This was achieved by step-by-step stretching in 0.1-g increments until the active contraction of the vessel ring to 100 mM KCl reached a plateau. The optimal resting tension of pulmonary veins of fetal lambs (0.29 ± 0.08 g; n = 15) was not significantly different from that of newborn lambs (0.30 ± 0.06 g; n = 13; P > 0.05). After the vessels were brought to their optimal resting tension, 1 h of equilibration was allowed. Then, indomethacin [10
5 M; an inhibitor
of cyclooxygenase (31)] and
nitro-L-arginine [104 M; an inhibitor
of nitric oxide synthase (18)] were administrated to eliminate
the possible involvement of endogenous prostanoids and
endothelium-derived nitric oxide (5, 8-10). Indomethacin (105 M) plus
nitro-L-arginine
(104 M) caused an increase
in resting tension by 0.78 ± 0.10 g
(n = 15) and 0.85 ± 0.13 g
(n = 13) for pulmonary veins of fetal and newborn lambs, respectively. These values are not significantly different (P > 0.05).
Effects of isoproterenol [a -adrenergic agonist (3)],
forskolin [a direct activator of adenyl cyclase (14)], and
8-bromoadenosine 3',5'-cyclic monophosphate
(8-BrcAMP) [a cell membrane-permeable analog of cAMP (15)]
were determined in vessels preconstricted with U-46619 [3 × 108 M; a stable
analog of thromboxane A2
(6)]. To determine whether the effect of
isoproterenol is mediated by -adrenergic receptors, the effect of
the agonist was examined both in the presence and absence of
propranolol [5 × 106 M; an antagonist of
-adrenergic receptors (3)]. Experiments with isoproterenol
were performed in the presence of hydrocortisone (3 × 105 M) and phentolamine (5 × 106 M) to block the
extraneuronal uptake and 
-adrenoceptor receptors, respectively (4,
30). All experiments mentioned above were performed in a parallel
manner. For each vessel ring, only one vasodilator was tested.
Measurement of cAMP.
Venous rings were incubated in modified Krebs-Ringer bicarbonate
solution (37°C, 95% O2-5%
CO2) in the presence of
indomethacin (105 M) and
nitro-L-arginine
(104 M) to eliminate the
involvements of endogenous prostanoids and endothelium-derived nitric
oxide (5, 8-10). To prevent the degradation of cAMP by
phosphodiesterases, isobutylmethylxanthine (3 × 104 M) was used (29). In
experiments with isoproterenol, hydrocortisone (3 × 105 M) and phentolamine (5 × 106 M) were present
to block the extraneuronal uptake and -adrenoceptor receptors,
respectively (4, 30).
8 M) or forskolin
(106 M) was added. The
vessel rings were rapidly frozen in liquid nitrogen at 2 and 10 min
after the administration of isoproterenol and forskolin, respectively.
Preliminary data showed that maximal accumulation of cAMP in the
vessels in response to isoproterenol and forskolin occurred at 2 and 10 min, respectively. Then, vessels were thawed in trichloroacetic acid
(6%), homogenized in glass with a motor-driven Teflon pestle,
sonicated for 5 s, and centrifuged at 13,000 g for 15 min. The supernatant was
extracted with four volumes of water-saturated diethyl ether and
lyophilized; the pellets were weighed. The lyophilized samples were
resuspended in 0.5 ml of sodium acetate buffer (0.05 M, pH 6.2), and
the content of cAMP was determined by using a cAMP kit (Biomedical
Technologies, Stoughton, MA). The content of cyclic nucleotide is
expressed as picomoles per milligram protein of the venous homogenate.
The protein content was determined by Bradford method by using bovine serum albumin as the standard (2).
Adenyl cyclase assay. The method of adenyl cyclase activity assay was similar to that used by Shaul et al. (27). Pulmonary veins were homogenized in 5 vol of ice-cold tris(hydroxymethyl)aminomethane (Tris) · HCl buffer (50 mM, pH 7.6) containing dithiothreitol (1 mM), EDTA (0.5 mM), isobutylmethylxanthine (1 mM), and phenymethylsulfonyl fluoride (1 mM). The homogenate was then filtered through two layers of gauze, and adenyl cyclase activity was determined on the resultant crude membrane preparation. Further purification of the membrane was not performed because isoproterenol-sensitive adenyl cyclase activity decreases with subsequent steps of smooth muscle membrane preparation (20). The protein concentrations of the homogenate were determined by Bradford method by using bovine serum albumin as the standard (2).
Pulmonary vessel membranes (20 µg protein) were incubated at 30°C for 10 min in 50 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer containing Tris · HCl (10 mM), dithiothreitol (0.1 mM), ATP (1 mM), MgCl2 (10 mM), creatine phosphate (12 mM), creatine phosphokinase (185 U/ml), ascorbic acid (0.5 mM), and isobutylmethylxanthine (1 mM) in the presence or absence of isoproterenol (3 × 108 M) and forskolin
(106 M). The total volume
was 150 µl. Preliminary experiments confirmed the linearity of adenyl
cyclase activity at the protein concentrations and incubation times.
The reaction was terminated by placing the assay tubes in a
boiling-water bath for 5 min. The samples were then centrifuged at
10,000 g for 15 min. The supernatant
were taken for the measurement of the cAMP formed by using a
radioimmunoassay kit (Biomedical Technologies). Adenyl cyclase activity
is expressed as picomoles cAMP per minute per milligram protein.
Drugs.
The following drugs were used (unless otherwise specified, all were
obtained from Sigma Chemical, St. Louis, MO):
L-ascorbic acid, 8-BrcAMP,
forskolin, hydrocortisone 21-hemisuccinate, indomethacin, isobutylmethylxanthine, isoproterenol,
nitro-L-arginine, phentolamine (Research Biochemicals International, Natick, MA), propranolol, and
U-46619 (9,11-dideoxy-11,9-epoxymethanoprostaglandin
prostagalndin F2
).
5 M) was
prepared in equal molar
Na2CO3.
This concentration of Na2CO3
did not significantly affect the pH of the solution in the organ
chamber. Isoproterenol was prepared in 0.1% ascorbic acid stock
solution to prevent oxidation of the agent. The other drugs were
prepared by using distilled water. Vessels were exposed to all
inhibitors and antagonists for at least 30 min before the effects of
-adrenoceptor agonists were tested.
Data analyses. Data are shown as means ± SE. When mean values of two groups were compared, Student's t-test for unpaired observations was used. When the mean values of the same group before and after stimulation were compared, Student's t-test for paired observations was used. Comparison of mean values of more than two groups from same vessel type was performed with one-way analysis of variance test with Student-Newman-Keuls test for post hoc testing of multiple comparison. All these analyses were performed by using a commercially available statistics package (SigmaStat, Jandel Scientific, San Rafael, CA). Statistical significance was accepted when the P value (2 tailed) was <0.05. In all experiments, n represents the number of animals.
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RESULTS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Organ chamber studies.
Effects of isoproterenol, forskolin, and 8-BrcAMP were examined after
vessel tension was raised with U-46619 (3 × 108 M). There were no
significant differences in the increase in tension induced by U-46619
among different vessel groups (Table 1).
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6 M) (Fig.
1). Forskolin also induced greater
relaxation of pulmonary veins of newborn lambs than those of fetal
lambs (Fig. 2). 8-BrcAMP induced similar
relaxation of all veins (Fig. 3).
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cAMP content. The basal intracellular content of cAMP was 25.3 ± 5.1 and 30.6 ± 3.6 pmol/mg protein for pulmonary veins of fetal and newborn lambs, respectively (n = 8 for each group). These values are not significantly different from each other (P > 0.05).
Isoproterenol (3 × 108 M) and forskolin
(106 M) induced a greater
increase in cAMP content of pulmonary veins of newborn lambs than that
of fetal lambs (Fig. 4).
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Adenyl cyclase activity.
The basal activity of adenyl cyclase was 8.76 ± 0.75 and 11.22 ± 1.23 pmol · mg1 · protein1 · min1
for the crude membrane preparations of pulmonary veins of fetal and
newborn lambs, respectively (n = 7 for
each group). They are not significantly different from each other
(P > 0.05).
8 M) and forskolin
(106 M) caused a greater
increase in adenyl cyclase activity of pulmonary veins of newborn than
those of fetal lambs (Fig. 5).
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DISCUSSION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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In the present study, isoproterenol induced greater relaxation of
pulmonary veins in newborn than in fetal lambs. The relaxation was
eliminated by propranolol. These results suggest that there is a
developmental increase in -adrenergic-agonist-mediated response in
pulmonary veins of the perinatal lambs.
A primary mechanism by which -adrenergic agonists cause vascular
smooth muscle to relax is by activating adenyl cyclase and subsequently
increasing production of cAMP (1, 19). In comparison to isoproterenol,
which activates adenyl cyclase by a receptor-mediated mechanism,
forskolin directly stimulates the activity of adenyl cyclase (14). In
our study, forskolin also caused greater relaxation of veins of newborn
lambs than those of fetal lambs. Furthermore, both isoproterenol and
forskolin caused a greater increase in the intracellular content of
cAMP and a greater increase in adenyl cyclase activity of pulmonary
venous preparations in newborn lambs than in fetal lambs. These results
suggest that a developmental increase in adenyl cyclase activity may
contribute to the differential responses of perinatal pulmonary veins
to isoproterenol.
In the present study, isoproterenol, at a concentration inducing comparable relaxation of veins as that of forskolin, caused a smaller increase in cAMP content and adenyl cyclase activity than did forskolin. Such a phenomenon has been observed in both pulmonary and nonpulmonary smooth muscles (11, 20, 27). The underlying mechanism is not well understood. One possible explanation is that there are multiple subcellular compartments for adenyl cyclases and cAMP. Some of the cAMP elevated after stimulation of adenyl cyclase with forskolin may be in subcellular compartments that are not accessible to the protein kinases involved in vasodilation (16, 32). Alternatively, isoproterenol may cause smooth muscle to relax by a mechanism that does not depend on cAMP. For instance, in porcine coronary arterial smooth muscle cells, isoproterenol may cause vasodilation by the stimulation of Ca2+-activated K+ channels, independent of cAMP (26).
cAMP induces vasodilation by multiple mechanisms, including inhibition of Ca2+ influx, stimulation of Ca2+ efflux, opening of Ca2+-dependent K+ channels, stimulation of Ca2+ uptake by sarcoplasmic reticulum, and inhibition of myosin phosphorylation (17). These effects are believed to be primarily mediated by cAMP-dependent protein kinase (1, 17). However, cAMP may cause smooth muscle to relax by other mechanisms such as activation of guanosine 3',5'-cyclic monophosphate-dependent protein kinase (12, 13). Authentic cAMP is a poor cell penetrant. Therefore, we used 8-BrcAMP, a cell membrane-permeable analog of cAMP (15), to examine the response of perinatal ovine pulmonary veins to cAMP. We found that all veins responded to the cAMP analog similarly, suggesting that the difference in isoproterenol- and forskolin-induced relaxation between pulmonary veins of fetal lambs and those of newborn lambs is not due to a differential response to cAMP.
In comparison to our knowledge of pulmonary arteries, our knowledge of
pulmonary veins is rather limited. In perinatal lungs, pulmonary veins
actively participate in regulation of the pulmonary vascular resistance
(9, 10, 22, 28). Thromboxane, platelet-activating factor, endothelin,
and hypoxia cause pulmonary veins of newborn lambs to constrict equally
or even more than do arteries (21, 23, 24). In fetal and newborn lambs,
relaxation of pulmonary veins induced by endothelium-derived nitric
oxide is developmentally regulated (9, 10, 28). Our present study
demonstrates that a developmental increase in
-adrenoceptor-agonist-mediated relaxation of pulmonary veins occurs
during the perinatal period. Furthermore, an increase in adenyl cyclase
activity may contribute to such a change.
It is worthy to note that the response of isolated vessels obtained
under in vitro conditions may not necessarily represent the response of
vessels under in vivo conditions. In our study, isoproterenol induced a
greater response of pulmonary veins of newborn lambs than that of fetal
lambs. This phenomenon was observed not only from vessel tension
studies but also from measurements of cAMP content and adenyl cyclase
activity. It is likely that it reflects a genuine developmental change
in -adrenergic-agonist-mediated response. We only examined the
response of the fourth generation of pulmonary veins of perinatal
sheep. Whether this phenomenon also occurs in veins of other
generations of the pulmonary venous tree and whether our results are
applicable to human in vivo remain to be explored.
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ACKNOWLEDGEMENTS |
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We thank Jean Morris for technical assistance and Monalisa Unutoa for secretarial assistance.
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FOOTNOTES |
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This study was supported by National Heart, Lung, and Blood Institute Grants HL-38438 and HL-47804 and by Le Center Hospitalier Universitaire Vaudois, Switzerland.
Address for reprint requests: Y. Gao, Harbor-UCLA Medical Center, Research and Education Institute, 1124 W. Carson St., RB-1, Torrance, CA 90502.
Received 30 June 1997; accepted in final form 15 December 1997.
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REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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|---|
1.
Barnes, P. J.,
and
S. F. Liu.
Regulation of pulmonary vascular tone.
Pharmacol. Rev.
47:
87-131,
1995[Medline].
2.
Bradford, M. M.
A rapid method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding.
Anal. Chem.
72:
249-254,
1973.
3.
Bylund, D. B.,
D. C. Eikenberg,
J. P. Hieble,
S. Z. Langer,
R. J. Lefkowitz,
K. P. Minneman,
P. B. Molinoff,
R. R. Ruffolo,
and
U. Trendelenburg.
International Union of Pharmacology nomenclature of adrenoceptors.
Pharmacol. Rev.
46:
121-136,
1994[Medline].
4.
Bylund, D. B.,
J. W. Regan,
J. E. Faber,
J. P. Hieble,
C. R. Triggle,
and
R. R. Ruffolo.
Vascular alpha-adrenoceptors: from the gene to the human.
Can. J. Physiol. Pharmacol.
73:
533-543,
1995[Medline].
5.
Cassin, S.
Role of prostaglandins and thromboxanes in the control of the pulmonary circulation in the fetus and newborn.
Semin. Perinatol.
4:
101-107,
1980[Medline].
6.
Coleman, R. A.,
P. P. A. Humphrey,
I. Kennedy,
G. P. Levy,
and
P. Lumley.
Comparison of the actions of U-46619, a prostaglandin H2-analogue, with those of prostaglandin H2 and thromboxane A2 on isolated smooth muscle preparations.
Br. J. Pharmacol.
73:
773-778,
1981[Medline].
7.
Fineman, J. R.,
S. J. Soifer,
and
M. A. Heymann.
Regulation of pulmonary vascular tone in the perinatal period.
Annu. Rev. Physiol.
57:
115-134,
1995[Medline].
8.
Gao, Y.,
H. Zhou,
B. O. Ibe,
and
J. U. Raj.
Prostaglandin E2 and I2 cause greater relaxations in pulmonary veins than in arteries of newborn lambs.
J. Appl. Physiol.
81:
2534-2539,
1996
9.
Gao, Y.,
H. Zhou,
and
J. U. Raj.
Endothelium-derived nitric oxide plays a larger role in pulmonary veins than in arteries of newborn lambs.
Circ. Res.
76:
559-565,
1995
10.
Gao, Y.,
H. Zhou,
and
J. U. Raj.
Heterogeneity in role of endothelium-derived NO in pulmonary arteries and veins of full-term fetal lambs.
Am. J. Physiol.
268 (Heart Circ. Physiol. 37):
H1586-H1592,
1995
11.
Gao, Y.,
H. Zhou,
J.-F. Tolsa,
H. Shen,
and
J. U. Raj.
Antenatal betamethasone therapy augments isoproterenol and prostaglandin E2-mediated relaxation of preterm ovine pulmonary veins.
Pediatr. Res.
42:
545-549,
1997[Medline].
12.
Jiang, H.,
J. L. Colbran,
S. H. Francis,
and
J. D. Corbin.
Direct evidence for cross-activation of cGMP-dependent protein kinase by cAMP in pig coronary arteries.
J. Biol. Chem.
267:
1015-1019,
1992
13.
Lincoln, T. M.,
T. L. Cornwell,
and
A. E. Taylor.
cGMP-dependent protein kinase mediates the reduction of Ca2+ by cAMP in vascular smooth muscle cells.
Am. J. Physiol.
258 (Cell Physiol. 27):
C399-C407,
1990
14.
Lincoln, T. M.,
and
V. Fisher-Simpson.
A comparison of the effects of forskolin and sodium nitroprusside on cyclic nucleotides and relaxation in the rat aorta.
Eur. J. Pharmacol.
101:
17-27,
1984[Medline].
15.
Meyer, R. B. J.,
and
J. P. Miller.
Analogs of cyclic AMP and cyclic GMP: general methods of synthesis and the relationship of structure to enzymic activity.
Life Sci.
14:
1019-1040,
1974[Medline].
16.
Morita, T.,
M. Ando,
K. Kihara,
H. Oshima,
S. Kondo,
and
Y. Tashima.
Dissociation of magnitude of relaxation from cyclic AMP levels in rabbit urinary bladder smooth muscles.
J. Smooth Muscle Res.
28:
121-128,
1992[Medline].
17.
Murray, K. J.
Cyclic AMP and mechanisms of vasodilation.
Pharmacol. Ther.
47:
329-345,
1990[Medline].
18.
Mülsch, A.,
and
R. Busse.
NG-nitro-L-arginine(N5-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine.
Naunyn Schmiedebergs Arch. Pharmacol.
341:
143-147,
1990[Medline].
19.
Nijkamp, F. P.,
F. Engels,
P. A. Henricks,
and
J. M. Van Oosterrhout.
Mechanisms of -adrenergic receptor regulation in lungs and its implications for physiological responses.
Physiol. Rev.
72:
323-367,
1992
20.
Popovich, K. J.,
C. Hiller,
A. Hough,
J. S. Norris,
and
L. E. Cornett.
Characterization of a -adrenergic receptor in porcine trachealis muscle.
Am. J. Physiol.
247 (Cell Physiol. 16):
C342-C349,
1984
21.
Raj, J. U.,
and
J. Anderson.
Pulmonary venous responses to thromboxane A2 analogue and atrial natriuretic peptide in lambs.
Circ. Res.
66:
496-502,
1990
22.
Raj, J. U.,
and
P. Chen.
Microvascular pressures measured by micropuncture in isolated perfused lamb lungs.
J. Appl. Physiol.
61:
2194-2201,
1986
23.
Raj, J. U.,
T. A. Hazinski,
and
R. D. Bland.
Effect of hypoxia on lung lymph flow in newborn lambs with left atrial hypertension.
Am. J. Physiol.
254 (Heart Circ. Physiol. 23):
H487-H493,
1988
24.
Raj, J. U.,
R. Hillyard,
P. Kaapa,
M. Gropper,
and
J. Anderson.
Pulmonary arterial and venous constriction during hypoxia in 3- to 5-wk-old and adult ferrets.
J. Appl. Physiol.
69:
2183-2189,
1990
25.
Rudolph, A. M.
Fetal and neonatal pulmonary circulation.
Annu. Rev. Physiol.
41:
383-395,
1979[Medline].
26.
Scornik, F. S.,
J. Codina,
L. Birnbaumer,
and
L. Toro.
Modulation of coronary smooth muscle KCa channels by Gs independent of phosphorylation by protein kinase A.
Am. J. Physiol.
265 (Heart Circ. Physiol. 34):
H1460-H1465,
1993
27.
Shaul, P. W.,
K. H. Muntz,
and
L. M. Buja.
Comparison of beta adrenergic receptor binding characteristics and coupling to adenylate cyclase in rat pulmonary artery versus aorta.
J. Pharmacol. Exp. Ther.
252:
86-92,
1990
28.
Steinhorn, R. H.,
F. C. Morin,
S. F. Gugino,
E. C. Giese,
and
J. A. Russell.
Developmental differences in endothelium-dependent responses in isolated ovine pulmonary arteries and veins.
Am. J. Physiol.
264 (Heart Circ. Physiol. 33):
H2162-H2167,
1993
29.
Thompson, W. J.
Cyclic nucleotide phosphodiesterases: pharmacology, biochemistry and function.
Pharmacol. Ther.
51:
13-33,
1991[Medline].
30.
Trendelenburg, U.
A kinetic analysis of the extraneuronal uptake and metabolism of catecholamine.
Rev. Physiol. Biochem. Pharmacol.
87:
33-115,
1980[Medline].
31.
Vane, J.,
and
R. Botting.
Inflammation and the mechanism of action of antiinflammatory drugs.
FASEB J.
1:
89-96,
1987[Abstract].
32.
Zhou, H. L.,
S. J. Newsholme,
and
T. J. Torphy.
Agonist-related differences in the relationship between cAMP content and protein kinase activity in canine trachealis.
J. Pharmacol. Exp. Ther.
261:
1260-1267,
1992
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, Veins of fetal lambs; 
, veins of fetal lambs treated with
propranolol (5 × 10
, veins of newborn lambs; 
, veins of newborn lambs treated
with propranolol (3 × 10
Significant
difference between veins of fetal and newborn lambs,
P < 0.05.
