Pearce, W.J., Hull, A.D., Long, D.M., White, C.R.
Effects of maturation on cyclic GMP-dependent vasodilatation in ovine basilar and carotid arteries.
Pediatric Research 1994 36:25-33The present experiments examine the effects of maturation on cGMP-mediated vasodilatation in 688 segments of common carotid (COM) and basilar (BAS) arteries taken from newborn (3-7 days old) and non-pregnant adult sheep. The main finding is that maximum efficacy for relaxation decreased with maturation in both artery types for the nitric oxide releasing vasodilators S-nitroso-N-acetyl-penacillamine (SNAP) and nitroglycerin. These decreases could not be explained by changes in the pD2 (-log ED50) concentrations for either vasodilator. Determination of the time course of cGMP responses to SNAP or nitroglycerin at 10 µM revealed that the peak cGMP responses to these agents (range: 5.3±0.8 to 8.3±1.6 pmol/mg protein) also did not vary significantly with age. However, cGMP attained peak values more rapidly in adult (COM: 50 sec, BAS 30 sec) than in newborn (COM: 60-80 sec, BAS 40-60 sec) segments and returned to baseline more slowly in newborn 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) than in adult (COM: 0.3±0.1, BAS: 1.7±0.2) segments. Despite these differences in cGMP time course however, rates of relaxation to SNAP and nitroglycerin did not vary significantly with age, indicating that the temporal relation between cGMP and relaxation is different in newborn and adult arteries. Together, these results suggest that the capacity of the cGMP pathway to produce relaxation is attenuated by maturation through changes possibly related to cGMP turnover.