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Greater β‐Adrenergic Vasodilation in Healthy Men Versus Women: Cyclooxygenase Suppresses Nitric Oxide
Author(s) -
Peltonen Garrett,
Johansson Rebecca,
Limberg Jacqueline,
Harrell John,
Ernst Brady,
Kellawan Jeremy,
Crain Meghan,
Eldridge Marlowe,
Sebranek Joshua,
Walker Benjamin,
Schrage William
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1053.4
Subject(s) - vasodilation , medicine , endocrinology , cyclooxygenase , brachial artery , nitric oxide , nitric oxide synthase , agonist , forearm , reactive hyperemia , blood pressure , receptor , chemistry , surgery , biochemistry , enzyme
Data suggest women exhibit greater β‐adrenergic receptor (β‐AR) mediated regulation of blood pressure than men. We tested the hypothesis that peripheral β‐AR vasodilation is greater in women, due in part to nitric oxide synthase (NOS) and cyclooxygenase (COX) signaling. In 22 healthy adults (10 men, 12 women; 24±2 yrs) forearm blood flow (FBF) was measured by Doppler ultrasound during graded brachial artery infusion of the β‐AR agonist isoproterenol (ISO: 3, 6, and 12 ng 100 ml lean tissue ‐1 min ‐1 ). Three ISO trials were performed: 1) ISO (control), 2) ISO with NOS or COX inhibition [L‐NMMA (n=10) or ketorolac (n=12), respectively, in counterbalanced order] followed by, 3) ISO with combined NOS + COX inhibition (double blockade – DB, n=22). Forearm vascular conductance was calculated (FVC = FBF/MAP) and the rise in FVC with ISO infusion (DFVC; infusion – baseline) quantified β‐AR vasodilation. Contrary to our hypothesis, DFVC with ISO was greater in men than women (p=0.02). L‐NMMA decreased DFVC from control (p=0.02) but did not eliminate the sex difference (p=0.01). Ketorolac increased DFVC above control (p<0.01), and abolished the sex‐difference (p=0.39). DB decreased DFVC below control (p=0.03) such that DFVC was again greater in men than women (p=0.01). We conclude: 1) β‐AR vasodilation is greater in young men vs women, 2) COX signaling limits β‐AR vasodilation more in women, and 3) COX appears to suppress NOS in both sexes, but more in women. These data are the first to demonstrate COX‐mediated restraint of β‐AR vasodilation in humans, and highlight sex differences in β‐AR control. Support: NIH R01 HL105820