Nitric Oxide and β-Adrenergic Mechanisms Modify Contractile Responses to Norepinephrine in Ovine Fetal and Newborn Cerebral Arteries

Abstract

Ovine fetal cerebral artcries exhibit an enhanced contractile response to norepinephrine (NH) compared with newborns and adults. It is possible that P-adrenergic receptors and/or nitric oxide (NO), a putative endothelium-dependent relaxing factor, differentially modulate cerebrovascular responsiveness to NE as a function of developmcnt. 'l'he present study evaluated the effect of thc P-adrenoceptor antagonist, propranolol, and the NO synthasc inhibitor, N~-nitro-I.-arginine methyl estcr (I,NAME), on the contractile response of isolated middle cerebral artery (MCA) and basilar artery (BA) to NIi during fetal development. MCAs isolated from four preterm fetal lambs (105 d of gestation), seven near-term fetal lambs (125-130 d of gestation), and eight newborn lambs (2-7 d of age) were evaluated using organ baths. BAS isolated from the near-term fetal and newborn lambs were also evaluated. Contractile reactivity of MCAs to NB dccreased significantly during fetal maturation as manifested by a marked decrease in F,,,,, (maximal relative contractile force generated) and an increase in EC,,, (F,,, -100 -+ 7,41 -+ 7, and 28 r 8% of KC1 contraction; HC,,,-0.14 + 0.03, 1.09 :+-0.36, and 1.07 + 0.22 pM for preterm fetus, near-term fetus, and newborn lamb MCAs, respectively, p 5 0.05). Propranolol treatment M) increased F,,,, (2-fold) only for newborn lamb MCAs. Pretreatnlent with LNAME (10 '' M) markedly enhanced rhc contractile T h e activation of the sympatho-adrenal axis is considered to be unimportant to the regulation of cerebral blood flow in adults (1, 2); however, such is not necessarily the case for the fetus and neonate. Activation of sympathetic nerves constricted cerebral arterioles and decreased cerebral blood flow in newborn and Letal animal models (3-6). In addition, fetal cerebral arteries, both in vivo and in vitro, exhibited cnhanced reactivity to the sympathetic neurotransmitter, norepinephrine (NE) (7-9). 'l'hese reports suggest that the neuroeffector system may be an important factor with respect to the developing cerebral response to NE (7-fold decrease in EC,, and 2-fold increase in F',,,,, p < 0.05) for near-term fetus MCAs, whereas preterm fetus and newborn lamb MCAs were unaffected by the inhibitor. 13.4s were unresponsive to NE except for near-term fetus BAS in the presence of LNAMIX. 'l'he eEcct of NO-synthase inhibition on NE contractility was dependent on developmental age, being prominent near term. The data suggest that, in the more mature fetus, NO, presumably derived from endothelium, bchaves as a functional antagonist to sympathetic vasoconstriction of the cerebrovasculature, and its apparent absence permits unrepressed sympathetic vasoconstriction in the premature brain. (Pediatr Hes 38: 237-242, 1995) Abbreviations NE:, norepinephrine NO, nitric oxide MCA, middle cerebral artery BA, basilar artery LNAME, N~-nitro-L-arginine methyl ester EC,,, effective drug concentration inducing 50% of maximal response F,,,, maximal force generated in response to drug circulation and indicate t...

Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

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