Abstract
In vitro studies have suggested that pulmonary arteries can exhibit a myogenic response and that this myogenic response may be potent during the perinatal period. However, whether a myogenic response can be demonstrated to exist in vivo and the potential role of the myogenic response on the regulation of pulmonary blood flow during fetal life is unknown. We hypothesized that an acute increase in pulmonary artery pressure resulting from partial compression of the ductus arteriosus (DA) in the fetus may simultaneously activate two opposing responses: 1) blood flow-induced vasodilation (owing to shear stress); and 2) pressure-induced vasoconstriction (owing to the myogenic response). To test this hypothesis, we studied the hemodynamic response to partial DA compression with and without inhibition of shear stress-induced vasodilation by nitric oxide synthase blockade in chronically prepared late-gestation fetal lambs. Without inhibition of nitric oxide synthase, pulmonary vascular resistance progressively decreased by 39 ± 5% during the DA compression period (p < 0.05). In contrast, DA compression after nitric oxide synthase inhibition caused left pulmonary artery blood flow to initially increase and then steadily decrease toward a plateau value, and caused pulmonary vascular resistance to progressively increase by 28 ± 4% above baseline (p < 0.05). The plateau value of pulmonary vascular resistance was reached in less than 5 min after the onset of DA compression. Left pulmonary artery blood flow after 10 min of partial DA compression did not change with the rise in pulmonary artery pressure; plateau values of pulmonary vascular resistance increased linearly with the increase in pulmonary artery pressure. These results support the hypothesis that the perinatal lung circulation has a potent myogenic response, and that this response may be masked in vivo under physiologic conditions by nitric oxide synthase activity. We speculate that the myogenic response may become a predominant regulatory mechanism of pulmonary vascular resistance when endothelium-dependent vasoreactivity is impaired, such as in persistent pulmonary hypertension of the newborn.
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Abbreviations
- DA :
-
ductus arterios
- LPA :
-
left pulmonary artery
- PaO 2 :
-
arterial O2 pressure
- L-NA :
-
nitro-L-arginine
- NOS :
-
nitric oxide synthase
- NO :
-
nitric oxide
- PAP :
-
pulmonary artery pressure
- PVR :
-
pulmonary vascular resistance
- AOP :
-
aortic pressure
- LAP :
-
left atrial pressure
- PPHN :
-
persistent pulmonary hypertension of the newborn
References
Rudolph AM, Heymann MA 1972 Pulmonary circulation in fetal lambs. Pediatr Res 6: 341–347.
Lewis AB, Heymann MA, Rudolph AM 1976 Gestational changes in pulmonary vascular responses in fetal lambs in utero. Circ Res 39: 536–541.
Teitel DF, Iwamoto H, Rudolph AM 1987 Effects of birth related events on central blood flow patterns. Pediatr Res 22: 557–566.
Soifer SJ, Loitz RD, Roman C, Heymann MA 1985 Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs. Am J Physiol 249:H570–H576.
Cassin S, Gause G, Davis T, TerRiet M, Baker R 1988 Do inhibitors of lipoxygenase and cyclooxygenase block neonatal hypoxic pulmonary vasoconstriction?. J Appl Physiol 66: 1779–1784.
Ivy DD, Kinsella JP, Abman SH 1994 Physiologic characterization of endothelin A and B receptor activity in the ovine fetal pulmonary circulation. J Clin Invest 93: 2141–2148.
Abman SH, Accurso FJ 1989 Acute effects of partial compression of ductus arteriosus on fetal pulmonary circulation. Am J Physiol 257:H626–H634.
Accurso FJ, Alpert B, Wilkening RB, Petersen RG, Meschia G 1986 Time-dependent response of fetal pulmonary blood flow to an increase in fetal oxygen tension. Respir Physiol 63: 43–52.
Abman SH, Accurso FJ 1991 Sustained fetal pulmonary vasodilation with prolonged atrial natriuretic factor and GMP infusions. Am J Physiol 260:H183–H192.
Johansson B 1989 Myogenic tone and reactivity: definitions based on muscle physiology. J Hypertens 7( suppl 4): S5–S8.
Bevan JA, Laher I 1991 Pressure and flow-dependent vascular tone. FASEB J 5: 2267–2273.
Henrion D, Terzi F, Matrougui K, Duriez M, Boulanger CM, Clucci-Guyon E, Babinet C, Briand P, Friedlander G, Poitevin P, Levy BI 1997 Impaired flow-induced dilation in mesenteric resistance arteries from mice lacking vimentin. J Clin Invest 100: 2909–2914.
Zimmermann PA, Knot HJ, Stevenson AS, Nelson MT 1997 Increased myogenic tone and diminished responsiveness to ATP-sensitive K+ channel openers in cerebral arteries from diabetic rats. Circ Res 81: 996–1004.
Skarsgard P, Van Breemen C, Laher I 1997 Estrogen regulates myogenic tone in pressurized cerebral arteries by enhanced basal release of nitric oxide. Am J Physiol 273:H2248–H2256.
Kulik TJ, Evans JN, Gamble WJ 1988 Stretch-induced contraction in pulmonary arteries. Am J Physiol 255:H1191–H1198.
Belik J 1994 Myogenic response in large pulmonary arteries and its ontogenesis. Pediatr Res 36: 34–40.
Madden JA, Al Tinawi A, Birks E, Keller PA, Dawson CA 1996 Intrinsic tone and distensibility of in vitro and in situ cat pulmonary arteries. Lung 174: 291–301.
Shirai M, Ninomiya I, Dada K 1991 Constrictor response of small pulmonary arteries to acute pulmonary hypertension during left atrial pressure elevation. Jpn J Physiol 41: 129–142.
Cornfield DN, Chatfield BA, McQueston JA, McMurtry IF, Abman SH 1992 Effects of birth-related stimuli on L-arginine-dependent pulmonary vasodilation in ovine fetus. Am J Physiol 262:H1474–H1481.
Cooke JP, Rossitch E, Andon NA, Loscalzo J, Dzau VJ 1991 Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator. J Clin Invest 88: 1663–1671.
Abman SH, Accurso FJ, Ward RM, Wilkening RB 1986 Adaptation of fetal pulmonary blood flow to local infusion of tolazoline. Pediatr Res 20: 1131–1135.
Anderson DF, Bissonette JM, Farber JJ, Thornburg KL 1981 Central shunt flows and pressures in the mature fetal lamb. Am J Physiol 241:H60–H66.
Hill MA, Falcone JC, Meininger GA 1990 Evidence for protein kinase C involvement in arteriolar myogenic reactivity. Am J Physiol 259:H1586–H1594.
Johnson PC 1986 Autoregulation of blood flow. Circ Res 58: 483–495.
Meininger GA, Trzeciakowski JP 1988 Vasoconstriction is amplified by autoregulation during vasoconstrictor-induced hypertension. Am J Physiol 254:H709–H718.
Belik J 1995 The myogenic response of arterial vessels is increased in fetal pulmonary hypertension. Pediatr Res 37: 196–201.
D'Angelo G, Davis MJ, Meininger GA 1997 Calcium and mechanotransduction of the myogenic response. Am J Physiol 273:H175–H182.
Lloyd TC, Juratsch CE 1986 Pulmonary hypertension induced with an intraarterial balloon: an alternate mechanism. J Appl Physiol 61: 746–751.
Juratsch CE, Grover RF, Rose CE, Reeves JT, Walby WF, Laks MM 1985 Reversal of reflex pulmonary vasoconstriction induced by main pulmonary arterial distension. J Appl Physiol 58: 1107–1114.
Juratsch CE, Emmanouillides GC, Thibeault DW, Baylen BG, Jengo JA, Laks MM 1980 Pulmonary arterial hypertension induced by distension of the main pulmonary artery in conscious newborn, young and adult sheep. Pediatr Res 14: 1332–1338.
Baylen BG, Emmanouillides GC, Juratsch CE, Yoshida Y, French WJ, Criley JM 1980 Main pulmonary artery distension: a potential mechanism for acute pulmonary hypertension in the human newborn infant. J Pediatr 96: 540–544.
Murao M, Onodera S, Homma T, Kataoka N, Takabori T, Marutani Y, Kobayashi T, Makino M 1969 Effects of occlusion and further distension of unilateral pulmonary artery with an inflatable balloon upon systemic and pulmonary hemodynamics. Jpn Heart J 10: 59–70.
Mombouli JV, Vanhoutte PM 1997 Endothelium-derived hyperpolarization factor(s): updating the unknown. Trends Pharmacol Sci 18: 252–256.
Brayden JE 1990 Membrane hyperpolarization is a mechanism of endothelium-dependent cerebral vasodilation. Am J Physiol 259:H668–H673.
Hecker M, Mülsch A, Bassence E, Busse R 1993 Vasoconstriction and increased flow: two principal mechanisms of shear stress-dependent endothelial autocoid release. Am J Physiol 265:H828–H833.
Frangos JA, Eskin SG, McIntire LV, Ives CL 1984 Flow effects on prostacyclin production by cultured human endothelial cells. Science 227: 1477–1479.
Shimokawa H, Flavahan NA, Lorenz RR, Vanhoutte PM 1988 Prostacyclin releases EDRF and potentiates its action in coronary arteries of the pigs. Br J Pharmacol 95: 1197–1203.
McQueston JA, Cornfield DN, McMurtry IF, Abman SH 1993 Effects of oxygen and exogenous L-arginine on endothelium-derived relaxing factor activity in the fetal pulmonary circulation. Am J Physiol 264:H865–H871.
Shaul PW, Wells LB 1994 Oxygen modulates NO production selectively in fetal pulmonary endothelial cells. Am J Respir Cell Mol Biol 11: 432–438.
McQueston JA, Kinsella JP, Ivy DD, McMurtry IF, Abman SH 1995 Chronic pulmonary hypertension in utero impairs endothelium-dependent vasodilation. Am J Physiol 268:H288–H294.
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Supported in part by grants from the National Institutes of Health (HL41012 and 46481) and the American Heart Association (Established Investigator Award to S.H.A.).
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Storme, L., Rairigh, R., Parker, T. et al. In Vivo Evidence for a Myogenic Response in the Fetal Pulmonary Circulation. Pediatr Res 45, 425–431 (1999). https://doi.org/10.1203/00006450-199903000-00022
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DOI: https://doi.org/10.1203/00006450-199903000-00022
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