β-Adrenergic-mediated vasodilation in young men and women: cyclooxygenase restrains nitric oxide synthase

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 310; no. 6; pp. H756 - H764
• Main Authors: Limberg, Jacqueline K, Johansson, Rebecca E, Peltonen, Garrett L, Harrell, John W, Kellawan, J Mikhail, Eldridge, Marlowe W, Sebranek, Joshua J, Schrage, William G
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 15.03.2016
• Subjects: Adrenergic beta-Agonists - pharmacology; Adult; Cyclooxygenase Inhibitors - pharmacology; Enzyme Inhibitors - pharmacology; Female; Forearm - blood supply; Humans; Infusions, Intra-Arterial; Integrative Cardiovascular Physiology and Pathophysiology; Isoproterenol - pharmacology; Ketorolac - pharmacology; Male; Microcirculation - drug effects; Microcirculation - physiology; Nitric Oxide Synthase - antagonists & inhibitors; omega-N-Methylarginine - pharmacology; Prostaglandin-Endoperoxide Synthases - physiology; Sex Factors; Ultrasonography, Doppler; Vasodilation - drug effects; Vasodilation - physiology; isoproterenol; skeletal muscle; prostaglandin; blood flow; sex differences
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00886.2015

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.