Effects of Maturation on Cyclic GMP-Dependent Vasodilation in Ovine Basilar and Carotid Arteries

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 ED,, concentrations for either vasodilator. Determination of the time course of cGMP responses to S-nitroso-Nacetyl-penicillamine or nitroglycerin at 10 FM revealed that the peak cGMP responses to these agents (range: 5.3 2 0.8 to 8.3 a 1.6 pmollmg 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, 4 M 0 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 In most arteries, vascular structure and function are immature at birth and change markedly during early postnatal life (1). In the cerebral circulation, this immaturity may be particularly important, because it may contribute to the high incidence of cerebrovascular complications observed in neonates (2, 3). Among the few studies that have directly examined maturational changes in cerebral arteries, however, most have found that vasoconstrictor reactivity is generally higher in immature than in mature cerebral arteries (1, 4-6). Thus, the high incidence of neonatal cerebrovascular complications seems not to be a consequence of a deficit in the ability of cerebral arteries to respond to vasoconstrictor stimuli. Alternatively, it remains possible that altered mechanisms of cerebral vasorelaxation may be involved. If Supported by PHs Grant HL11347 and Grant 92-293A from the American Heart Association.higher in newborn (COM: 1.0 -' 0.1; BAS: 3.3 0.5 pmol/mg of protein) than in adult (COM: 0.3 2 0.1; BAS: 1.7 ? 0.2 pmollmg 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. Abbreviations ANOVA, analysis of variance cGMP, cyclic GMP pD,, the negative logarithm of the concentration of an agent that produces half its maximal effect SNAP, S-nitroso-N-acetyl-penicillamine NG, nitroglycerin newborn arteries have a greater propensity to relax, they may be less capable of resisting the vascular injury and rupture often associated with insults, such as asphyxia and transient hypertension, that markedly elevate cerebral perfusion. Me...

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