title: β-Adrenergic-mediated vasodilation in young men and women: cyclooxygenase restrains nitric oxide synthase.
abstract: We tested the hypothesis that women exhibit greater vasodilator responses to β-adrenoceptor stimulation compared with men. We further hypothesized women exhibit a greater contribution of nitric oxide synthase and cyclooxygenase to β-adrenergic-mediated vasodilation compared with men. Forearm blood flow (Doppler ultrasound) was measured in young men (n = 29, 26 ± 1 yr) and women (n = 33, 25 ± 1 yr) during intra-arterial infusion of isoproterenol (β-adrenergic agonist). In subset of subjects, isoproterenol responses were examined before and after local inhibition of nitric oxide synthase [N(G)-monomethyl-l-arginine (l-NMMA); 6 male/10 female] and/or cyclooxygenase (ketorolac; 5 male/5 female). Vascular conductance (blood flow ÷ mean arterial pressure) was calculated to assess vasodilation. Vascular conductance increased with isoproterenol infusion (P < 0.01), and this effect was not different between men and women (P = 0.41). l-NMMA infusion had no effect on isoproterenol-mediated dilation in men (P > 0.99) or women (P = 0.21). In contrast, ketorolac infusion markedly increased isoproterenol-mediated responses in both men (P < 0.01) and women (P = 0.04) and this rise was lost with subsequent l-NMMA infusion (men, P < 0.01; women, P < 0.05). β-Adrenergic vasodilation is not different between men and women and sex differences in the independent contribution of nitric oxide synthase and cyclooxygenase to β-mediated vasodilation are not present. However, these data are the first to demonstrate β-adrenoceptor activation of cyclooxygenase suppresses nitric oxide synthase signaling in human forearm microcirculation and may have important implications for neurovascular control in both health and disease.
authors.affiliation: Department of Kinesiology, University of Wisconsin, Madison, Wisconsin;
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Limberg
authors.affiliation: Department of Kinesiology, University of Wisconsin, Madison, Wisconsin;
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Johansson
authors.affiliation: Department of Kinesiology, University of Wisconsin, Madison, Wisconsin;
authors.forename: Garrett L
authors.initials: GL
authors.lastname: Peltonen
authors.affiliation: Department of Kinesiology, University of Wisconsin, Madison, Wisconsin;
authors.forename: John W
authors.initials: JW
authors.lastname: Harrell
authors.affiliation: Department of Kinesiology, University of Wisconsin, Madison, Wisconsin;
authors.forename: J Mikhail
authors.initials: JM
authors.lastname: Kellawan
authors.affiliation: Department of Kinesiology, University of Wisconsin, Madison, Wisconsin; Department of Pediatrics, University of Wisconsin, Madison, Wisconsin; and.
authors.forename: Marlowe W
authors.initials: MW
authors.lastname: Eldridge
authors.affiliation: Department of Anesthesiology, University of Wisconsin, Madison, Wisconsin.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Sebranek
authors.affiliation: Department of Kinesiology, University of Wisconsin, Madison, Wisconsin; wschrage@education.wisc.edu.
authors.forename: William G
authors.initials: WG
authors.lastname: Schrage
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007261:Infusions, Intra-Arterial; D007545:Isoproterenol / Q000494:pharmacology*; D020910:Ketorolac / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D012737:Sex Factors; D018608:Ultrasonography, Doppler; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D007545:Isoproterenol; D020910:Ketorolac
keywords: blood flow; isoproterenol; prostaglandin; sex differences; skeletal muscle