Maturational changes in endothelium-derived nitric oxide-mediated relaxation of ovine pulmonary arteries

Endothelium-derived nitric oxide (EDNO) modulates the responses of pulmonary vasculature. The present study was designed to determine EDNO-mediated responses of pulmonary arteries (PA) of term fetal, newborn, and adult sheep. Vessel rings were suspended in organ chambers and their isometric tension was recorded. In vessels preconstricted with endothelin-1, acetylcholine had no effect on fetal PA but caused a greater endothelium-dependent relaxation in adult PA than in newborn PA. In vessels without endothelium, nitric oxide and 8-bromo-cGMP caused greater relaxation in adult PA than in newborn PA while causing the least relaxation in fetal PA. Acetylcholine had no effect on cGMP content in fetal PA but caused a greater endothelium-dependent increase in cGMP content in adult PA than in newborn PA. In vessels without endothelium, nitric oxide caused a smaller increase in cGMP content of fetal PA than of newborn PA while causing the greatest increase in cGMP of adult PA. These results demonstrate an age-dependent increase in EDNO-mediated responses of ovine pulmonary arteries. A change in receptor and/or receptor coupling, in soluble guanylate cyclase activity, and in cGMP responsiveness of vascular smooth muscle may contribute to the phenomenon.