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 int rapulmonary arteries after exposure of piglets to chronic hypobaric hy poxia (CHH) from 0 to 2.5, 3 to 6, or 14 to 17 days of age. CHH inhibi ted the postnatal development of endothelium-dependent vasorelaxation to acetylcholine (ACh) and the calcium ionophore A-23187. Basal accumu lation of guanosine 3', 5'-cyclic monophosphate (cGMP) was unaffected, but cGMP response to ACh was inhibited. Endothelium-independent relax ation to nitric oxide (NO) and zaprinast (a phosphodiesterase inhibito r) was also inhibited, but cGMP accumulation in response to these agon ists was normal. The ability of sodium nitroprusside (SNP) to cause va sorelaxation and increase cGMP accumulation was unaffected. Contractil e responses to potassium chloride and prostaglandin F-2 alpha (PGF(2 a lpha)) were similar to normal after exposure from birth and 3 days and were decreased in the older group, but the ability of N-G-monomethyl- Larginine acetate to increase PGF(2 alpha)-induced contractions decrea sed. 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 inv olved in the release of NO and the effectiveness of cGMP.