MATURATION OF THE CONTRACTILE RESPONSE AND ITS ENDOTHELIAL MODULATION IN NEWBORN PORCINE INTRAPULMONARY ARTERIES

Pulmonary vascular reactivity is thought to be greater in the newborn than adult lung. To determine the influence of the endothelium on smooth muscle cell contractility, responses of rings of isolated intrapulmonary arteries were studied from pigs at birth aged <2 h, 2 d, 3 d, and 10 d (n = 4 per age group) and from eight adult animals. At birth, the response to KCl (25 mM) and prostaglandin F-2 alpha(PGF(2 alpha) (3 mu M) but not histamine (0.1 mM) was greater in rings with endothelium (E+) than without (E-). The response to PGF(2 alpha) decreased between birth and 3 d by which time the contraction was less in E+ rings than E-, but L-nitro monomethyl arginine augmented contraction at all ages. In the immature piglets, the response to phenylephrine was less in E+ rings than E-, an effect which was reversed by L-N-omega-nitro-L-arginine methyl ester. The response to all contractile agonists increased between 10 d and adulthood. The concentration of plasma endothelin-1 was determined in all animals by RIA and was higher at birth than at 3 d or later. In summary, 1) at birth, endothelium enhanced contractility, when plasma endothelin was greatest, but released NO in the presence of phenylephrine and PGF(2 alpha); 2) contractile response to all agonists was small at birth; and 3) a complex interaction existed between the contractile agonist and the effect of endothelial maturation. This study suggests that excessive reactivity in the newborn pulmonary vasculature may be due to immaturity of mechanisms determining endothelium-dependent arterial relaxation, but not to an excessive contractile response.