Role of the alpha2-adrenoceptors on the pulmonary circulation in the ovine fetus

Abstract

Recent in vitro studies reported that nitric oxide release and pulmonary vasorelaxation can be mediated by endothelial α2-adrenoceptor activation. As norepinephrine (α1,α2-, and β1-adrenoceptor agonist) was found to induce pulmonary vasodilation in the ovine fetus, we hypothesized that α2-adrenoceptors may modulate basal pulmonary vascular tone and mediate the vascular effect of norepinephrine during fetal life. To determine the role of α2-adrenoceptors and the mechanisms of norepinephrine-mediated vasodilation in the fetal pulmonary circulation, we tested, in chronically prepared late-gestation fetal lambs, the hemodynamic response to 1) yohimbine (α2 antagonist); 2) UK 14,304 (α2 agonist) with and without L-nitro-arginine (nitric oxide synthase inhibitor); and 3) norepinephrine infusion with and without yohimbine. We found that yohimbine increased mean pulmonary artery pressure by 15% (p < 0.05), decreased pulmonary flow by 22% (p < 0.01), and increased pulmonary vascular resistance by 51% (p < 0.01). UK 14,304 increased pulmonary flow by 145% (p < 0.01) and decreased pulmonary vascular resistance by 58% (p < 0.01). L-Nitro-arginine abolished the UK 14,304-mediated pulmonary vasodilation. Norepinephrine (0.5 μg·kg-1·min-1) increased both pulmonary flow by 61% (p < 0.01) and pulmonary arterial pressure by 13% (p < 0.01) and decreased pulmonary vascular resistance by 33% (p < 0.01). Yohimbine abolished the norepinephrine-induced pulmonary vasodilation. This study suggests that 1) a basal α2-adrenoceptor activation-induced pulmonary vasodilation exists during fetal life; 2) the pulmonary vascular effects of α2-adrenoceptor activation are related at least in part to nitric oxide production; and 3) the norepinephrine-mediated pulmonary vasodilation involves α2-adrenoceptor activation. As a surge of norepinephrine exists at birth, we speculate that norepinephrine and endothelial α2-adrenoceptor activation may play a significant role in pulmonary vasodilation at birth.