Exogenous Norepinephrine Constricts Cerebral Arterioles via α2-Adrenoceptors in Newborn Pigs

Abstract

The purpose of this study was to determine whether exogenous norepinephrine mediates cerebrovascular constriction via α1- or α2-adrenoceptors in anesthetized neonatal pigs. Diameters of pial arterioles in anesthetized piglets, 1–6 days old, were investigated using a “closed” cranial window. We examined constrictor effects of norepinephrine on pial arterioles in the absence and presence of relatively selective α1,- (prazosin) and α2-(yohimbine) adrenoceptor antagonists (1 mg/kg i.v.). Yohimbine and prazosin inhibited pial arteriolar constriction induced by topical application of clonidine and phenylephrine (10−6 and 10−4 M, respectively), and yohimbine did not affect the response to topical phenylephrine. In one group diameter was 188 ± 13 (mean ± SEM) μm during control and 146 ± 12 (μm during 10−5 M norepinephrine (22 ± 5% constriction). Following yohimbine the same vessels did not constrict significantly. In another group 10−5 M norepinephrine constricted arterioles by 22 ± 5%, and this response was unaffected by prazosin (24 ± 5% constriction). We conclude that pial arterioles are responsive to both α1- and α2-adrenoceptor agonists, that intravenous administration of prazosin and yohimbine results in these drugs crossing the blood–brain barrier and inhibiting constrictor effects of agonists, and that norepinephrine constricts pial arterioles predominantly via α2-adrenoceptors.