Endothelium-dependent relaxations of piglet pulmonary arteries augment with maturation

Abstract

To determine whether maturation alters endothelium-dependent responses in porcine pulmonary arteries, rings, with and without endothelium, of small pulmonary arteries taken from piglets of 3, 10, and 30 d of age were suspended in organ chambers filled with buffered salt solution, bubbled with 95% O2-5% CO2, and maintained at 37°C. These studies were performed in the presence of indomethacin (10-5 M) to inhibit prostaglandin synthesis. In rings without endothelium, potassium chloride (10-2 to 8.5 x 10-2 M) and histamine (10-9 to 10-5 M) caused concentration-dependent contractions. When normalized to maximal contractions achieved to each agonist, the concentration-effect curves to potassium chloride and histamine in rings without endothelium were similar at each age. Rings with endothelium showed a progressive shift to the right of the concentration-effect curve to histamine, possibly secondary to an increase in the basal release of, or responsiveness to, the endothelium-derived relaxing factor with maturation. Relaxations to sodium nitroprusside (10-9 to 10-5 M) were unaffected by age. In precontracted rings, acetylcholine (10-9 to 10-6 M), bradykinin (10-10 to 10-6 M), and the calcium ionophore A23187 (10-9 to 10-6 M) caused relaxations in rings with endothelium, but not in those without endothelium, which were greater at 10 and 30 d compared to 3 d; further augmentation at 30 d compared to 10 d was not observed. In rings without endothelium, changes in the responsiveness to nitric oxide (10-9 to 10-5 M), one of the proposed endothelium-derived relaxing factors, with age were comparable to those observed with endothelium-dependent relaxing agents. These studies demonstrate that endothelium-dependent relaxations increase with age, possibly due to changes in sensitivity of the smooth muscle to the endothelium-derived relaxing factor.