Chronic hypoxia inhibits postnatal maturation of porcine intrapulmonary artery relaxation.
Neonatal pulmonary hypertension is associated with increased pulmonary vascular reactivity. We studied the responses of isolated porcine intrapulmonary arteries after exposure of piglets to chronic hypobaric hypoxia (CHH) from 0 to 2.5, 3 to 6, or 14 to 17 days of age. CHH inhibited the postnatal development of endothelium-dependent vasorelaxation to acetylcholine (ACh) and the calcium ionophore A-23187. Basal accumulation of guanosine 3', 5'-cyclic monophosphate (cGMP) was unaffected, but cGMP response to ACh was inhibited. Endothelium-independent relaxation to nitric oxide (NO) and zaprinast (a phosphodiesterase inhibitor) was also inhibited, but cGMP accumulation in response to these agonists was normal. The ability of sodium nitroprusside (SNP) to cause vasorelaxation and increase cGMP accumulation was unaffected. Contractile responses to potassium chloride and prostaglandin F2 alpha (PGF2 alpha) were similar to normal after exposure from birth and 3 days and were decreased in the older group, but the ability of NG-monomethyl-L-arginine acetate to increase PGF2 alpha-induced contractions decreased. Thus exposure of newborn piglets to CHH causes 1) no increase in contractile responses and 2) impairment of endothelium-dependent and -independent relaxation by impairing signal transduction mechanisms involved in the release of NO and the effectiveness of cGMP.
Tulloh
R M
RM
Developmental Pharmacology and Vascular Biology Unit, Institute of Child Health, London, United Kingdom.
Hislop
A A
AA
Boels
P J
PJ
Deutsch
J
J
Haworth
S G
SG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001274:Atmospheric Pressure; D000001:Calcimycin / Q000494:pharmacology; D002908:Chronic Disease; D006152:Cyclic GMP / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D006321:Heart / Q000033:anatomy & histology; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology*; D011688:Purinones / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation; D014666:Vasomotor System / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D011688:Purinones; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000001:Calcimycin; D011189:Potassium Chloride; D015237:Dinoprost; C011145:zaprinast; D006152:Cyclic GMP; D000109:Acetylcholine