title: Gender-dependent modulation of alpha 1-adrenergic responses in rat mesenteric arteries.
abstract: The purpose of this study was to test the hypothesis that pathways modulating vasoconstriction in rat mesenteric resistance arteries are gender dependent. Net contractile responses to phenylephrine were significantly increased by endothelium disruption in arteries from males but not females. This gender-dependent effect was stimulus specific, because disruption of endothelium increased reactivity to serotonin comparably in arteries from both genders. Ovariectomy unmasked an increase in net alpha(1)-adrenergic contractile responsiveness after endothelium disruption, suggesting alpha(1)-adrenergic-stimulated production of endothelial vasodilators is suppressed in control females by gonadal sex steroids. Production of modulatory endothelium-derived vasodilators in males is balanced by production of vasoconstricting arachidonic acid metabolites. This was revealed by decreased alpha(1)-adrenergic contractile responses in arteries from males after pretreatment with indomethacin or the cyclooxygenase-1 selective inhibitor SC-560. The indomethacin-induced effect persisted after endothelium disruption, indicating smooth muscle as the source of cyclooxygenase-1-derived vasoconstrictors and was attenuated after orchiectomy. This study indicates gender differences in the expression of two pathways modulating alpha(1)-adrenergic sensitivity in mesenteric arteries: an endothelium-dependent vasodilator pathway and a balancing smooth muscle cyclooxygenase-1-dependent vasoconstrictor pathway. One consequence of these differences is that endothelial damage produces a selective increase in alpha(1)-adrenergic agonist reactivity in arteries from males.
authors.affiliation: Center for Cardiovascular Sciences, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
authors.forename: Alyson P
authors.initials: AP
authors.lastname: McKee
authors.forename: Dee A
authors.initials: DA
authors.lastname: Van Riper
authors.forename: Cathy A
authors.initials: CA
authors.lastname: Davison
authors.forename: Harold A
authors.initials: HA
authors.lastname: Singer
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008638:Mesenteric Arteries / Q000502:physiology*; D009919:Orchiectomy; D010052:Ovariectomy; D010656:Phenylephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012727:Sex Characteristics; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D012701:Serotonin; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D007213:Indomethacin