title: Prolactin induces regional vasoconstriction through the beta2-adrenergic and nitric oxide mechanisms.
abstract: Prolactin has been associated with many effects and has been implicated in the pathogenesis of pregnancy-related hypertensive disorders, although little is known about its vascular effects. The present study was designed to determine the primary effect of prolactin on regional vascular beds and the mechanisms involved. In 37 anesthetized pigs, the infusion of 0.17 mug/kg min of prolactin at constant heart rate and arterial pressure decreased coronary, mesenteric, renal, and iliac blood flow. This response was graded in further five pigs by increasing the infused dose of the hormone between 0.017 and 1 mug/kg min. In 22 of the 37 pigs, blockade of cholinergic receptors (five pigs) and of alpha-adrenoceptors (five pigs) did not affect the prolactin-induced vascular response, which was abolished by blockade of beta(2)-adrenoceptors (five pigs) and by blockade of vascular nitric oxide (NO) synthase (seven pigs). In 15 of the 37 pigs the increases in measured blood flows caused by iv infusion of isoproterenol (five pigs) and by intraarterial administration of acetylcholine (five pigs) and of sodium nitroprusside (five pigs) were significantly reduced by infusion of prolactin. Moreover, the treatment of porcine aortic endothelial cells by prolactin caused a reduction of NO production and of the phosphorylation of ERK, Akt, and p38, which was prevented by the concomitant treatment by the beta(2)-adrenergic agonist albuterol. The present study showed that iv infusion of prolactin primarily caused coronary, mesenteric, renal, and iliac vasoconstriction. These effects were brought about by the inhibition of a vasodilatory beta(2)-adrenergic receptor-mediated effect related to the NO intracellular pathway.
authors.affiliation: Laboratorio di Fisiologia, Dipartimento di Medicina Clinica e Sperimentale, Facoltà di Medicina e Chirurgia, Università del Piemonte Orientale A. Avogadro, via Solaroli 17, I-28100 Novara, Italy. molinari@med.unipmn.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Molinari
authors.forename: Elena
authors.initials: E
authors.lastname: Grossini
authors.forename: David A S G
authors.initials: DA
authors.lastname: Mary
authors.forename: Francesca
authors.initials: F
authors.lastname: Uberti
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Flavio
authors.initials: F
authors.lastname: Ribichini
authors.forename: Nicola
authors.initials: N
authors.lastname: Surico
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vacca
mesh_terms: D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000502:physiology; D002078:Butoxamine / Q000494:pharmacology; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism* / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D018343:Receptors, Adrenergic, beta-2; D002078:Butoxamine; D009569:Nitric Oxide; D011388:Prolactin; D019001:Nitric Oxide Synthase; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester