EFFECTS OF MATURATION ON CYCLIC GMP-DEPENDENT VASODILATION IN OVINE BASILAR AND CAROTID ARTERIES

The present experiments examine the effects of maturation on cyclic GM P (cGMP)-mediated vasodilation in 688 segments of common carotid (COM) and basilar (BAS) arteries taken from newborn (3- to 7-d-old) and non pregnant adult sheep. The main finding is that maximum efficacy for re laxation decreased with maturation in both artery types for the nitric oxide releasing vasodilators S-nitroso-N-acetyl-penicillamine and nit roglycerin. These decreases could not be explained by changes in the - log ED(50) concentrations for either vasodilator. Determination of the time course of cGMP responses to S-nitroso-N-acetyl-penicillamine or nitroglycerin at 10 mu M revealed that the peak cGMP responses to thes e agents (range: 5.3 +/- 0.8 to 8.3 +/- 1.6 pmol/mg of protein) also d id not vary significantly with age. However, cGMP attained peak values more rapidly in adult (COM: 50 s; BAS 30 s) than in newborn (COM: 60- 80 s: BAS, 40-60 s) segments and returned to baseline more slowly in n ewborn than in adult segments, suggesting that maturation accelerates cGMP turnover. Correspondingly, baseline levels of cGMP were higher in newborn (COM: 1.0 +/- 0.1; BAS: 3.3 +/- 0.5 pmol/mg of protein) than in adult (COM: 0.3 +/- 0.1; BAS: 1.7 +/- 0.2 pmol/mg of protein) segme nts. Despite these differences in cGMP time course, rates of relaxatio n in response to S-nitroso-N-acetyl-penicillamine and nitroglycerin di d not vary significantly with age, indicating that the temporal relati on between cGMP and relaxation is different in newborn and adult arter ies. Together, these results suggest that the capacity of the cGMP pat hway to produce relaxation is attenuated by maturation through changes possibly related to cGMP turnover.