title: 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 alpha2-adrenoceptor activation. As norepinephrine (alpha1-,alpha2-, and beta1-adrenoceptor agonist) was found to induce pulmonary vasodilation in the ovine fetus, we hypothesized that alpha2-adrenoceptors may modulate basal pulmonary vascular tone and mediate the vascular effect of norepinephrine during fetal life. To determine the role of alpha2-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 (alpha2 antagonist); 2). UK 14304 (alpha2 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 14304 increased pulmonary flow by 145% (p < 0.01) and decreased pulmonary vascular resistance by 58% (p < 0.01). l-Nitro-arginine abolished the UK 14304-mediated pulmonary vasodilation. Norepinephrine (0.5 microg x kg(-1)x 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 alpha2-adrenoceptor activation-induced pulmonary vasodilation exists during fetal life; 2). the pulmonary vascular effects of alpha2-adrenoceptor activation are related at least in part to nitric oxide production; and 3). the norepinephrine-mediated pulmonary vasodilation involves alpha2-adrenoceptor activation. As a surge of norepinephrine exists at birth, we speculate that norepinephrine and endothelial alpha2-adrenoceptor activation may play a significant role in pulmonary vasodilation at birth.
authors.affiliation: Department of Perinatal Medicine, Centre Hospitalier et Universitaire, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Magnenant
authors.forename: Sophie
authors.initials: S
authors.lastname: Jaillard
authors.forename: Philippe
authors.initials: P
authors.lastname: Deruelle
authors.forename: Veronique
authors.initials: V
authors.lastname: Houfflin-Debarge
authors.forename: Yvon
authors.initials: Y
authors.lastname: Riou
authors.forename: Serge
authors.initials: S
authors.lastname: Klosowski
authors.forename: Laurent
authors.initials: L
authors.lastname: Storme
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012756:Sheep; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D019335:Nitroarginine; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D019001:Nitric Oxide Synthase; D009638:Norepinephrine