POSTNATAL ADRENOCEPTOR MATURATION IN PORCINE INTRAPULMONARY ARTERIES

The effect of postnatal ape on norepinephrine-induced alpha(2)-adrenor eceptor-mediated release of endothelium-derived relaxing factor in por cine intramuscular pulmonary arteries was studied. Rings of pulmonary artery from fetal, newborn, 3-d-, 10-d-, 9-wk-, and 15-wk-old pigs wit h and without endothelium were suspended for isometric force measureme nt in Krebs-Ringer bicarbonate solution (37 degrees C, 95% O-2-5% CO2) . In 15- and 10-wk-old pigs, norepinephrine increased tone in arteries with and without endothelium but produced relaxations at high concent rations only in arteries with endothelium. These relaxations were not inhibited by the alpha(1)-antagonist prazosin but were completely abol ished by the alpha(2)-antagonist yohimbine and the inhibitor of nitric oxide release N-omega-nitro-L-arginine methyl ester. This confirms th at the norepinephrine-induced relaxations were due to alpha(2)-mediate d release of endothelium-derived relaxing factor. Arteries from only 5 0% of the 10-d-old animals showed endothelium-dependent relaxations, a nd at 3 d of age and younger no relaxations were seen. In animals less than 10 d old, only some of the vessels contracted to norepinephrine and the contractile response was diminished compared with 15-wk-old an imals, whereas the response to prostaglandin F-2 alpha and histamine w as similar in the neonatal group (newborn, 3 d old, and 10 d old). Thi s group showed a dose-dependent relaxation to nitric oxide, with 10-d- old animals more sensitive to nitric oxide than newborn animals. Thus, maturational changes occur in adrenergic-mediated contraction, in the modulation of contractility by endothelial alpha(2)-adrenoreceptors a nd in the response to nitric oxide.