Abstract
ABSTRACT: The present experiments examine the effects of maturation on cyclic GMP (cGMP)-mediated vasodilation in 688 segments of common carotid (COM) and basilar (BAS) arteries taken from newborn (3− to 7-d-old) and nonpregnant 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-penicillamine and nitroglycerin. These decreases could not be explained by changes in the -log ED50 concentrations for either vasodilator. Determination of the time course of cGMP responses to S-nitroso-N-acetyl-penicillamine 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 of protein) also did 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 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 pmol/mg of protein) than in adult (COM: 0.3 ±0.1; BAS: 1.7 ± 0.2 pmol/mg of protein) segments. Despite these differences in cGMP time course, rates of relaxation in response to S-nitroso-N-acetyl-penicillamine 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.
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Pearce, W., Hull, A., Long, D. et al. Effects of Maturation on Cyclic GMP-Dependent Vasodilation in Ovine Basilar and Carotid Arteries. Pediatr Res 36 (Suppl 1), 25–33 (1994). https://doi.org/10.1203/00006450-199407001-00005
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DOI: https://doi.org/10.1203/00006450-199407001-00005