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 KC1 (25 mM) and prostaglandin F,, (PGF,,) (3 pM) but not histamine (0.1 mM) was greater in rings with endothelium (E+) than without (E-). The response to PGF,, 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-Nwnitro-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, I ) at birth, endothelium enhanced contractility, when plasma endothelin was greatest, but released NO in the presence of phenylephrine and PGF,,; 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. (Pediatr Res 38: [25][26][27][28][29]1995) Abbreviations PGF,,, prostaglandin F, , PE, phenylephrine L-NAME, N"-nitro-L-arginine methyl ester L-NMMA, L-nitro monomethyl arginine EDRF, endothelium-derived relaxing factor NO, nitric oxide At birth, the pulmonary arterial pressure and resistance are high and decrease rapidly during the first hours after birth due to structural (1-3) and functional (4, 5) remodeling. The mechanisms responsible for these changes are not fully elucidated, but EDRF is known to play a role. EDRF (6-8) is released from the lungs of fetal and newborn animals (9-11).It helps reduce basal tone in utero and contributes to the postnatal fall in pulmonary vascular resistance. However, endothelium-dependent relaxation to acetylcholine is absent at birth in the porcine lung and does not appear until the third day of life (5). In the ovine lung, endothelial-dependent relaxation in response to acetylcholine, ADP, and calcium ionophore (A23187) is minimal in utero and at birth and increases rapidly during the first week of life (12). These observations suggest that immediately after birth the interactions between the endothelium and the underlying smooth muscle may be different from those in adult porcine pulmonary vasculature. In mature blood vessels, the endothelium is thought to play an important role in the control of vascular tone through a balance between EDRF such as NO (lo), prostacyclin (13), bradykinin (14), the endothelium-...