Exercise vasodilation is greater in women: contributions of nitric oxide synthase and cyclooxygenase

Abstract

Purpose We hypothesized exercise vasodilation would be greater in women due to nitric oxide synthase (NOS) and cyclooxygenase (COX) signaling. Methods 45 healthy adults (23 women, W, 22 men, M, 26 ± 1 years) completed two 10-min trials of dynamic forearm exercise at 15 % intensity. Forearm blood flow (FBF; Doppler ultrasound), arterial pressure (brachial catheter), and forearm lean mass were measured to calculate relative forearm vascular conductance (FVCrel) = F BF 100 mmHg−1 100 g−1 lean mass. Local intra-arterial infusion of L-NMMA or ketorolac acutely inhibited NOS and COX, respectively. In Trial 1, the first 5 min served as control exercise (CON), followed by 5 min of L-NMMA or ketorolac over the last 5 min of exercise. In Trial 2, the remaining drug was infused during 5–10 min, to achieve combined NOS–COX inhibition (double blockade, DB). Results Are mean ± SE. Women exhibited 29 % greater vasodilation in CON (AFVCrel, 19 ± 1 vs. 15 ± 1, p = 0.01). L-NMMA reduced AFVCrel (p < 0.001) (W: Δ −2.3 ± 1.3 vs. M: Δ −3.7 ± 0.8, p = 0.25); whereas, ketorolac modestly increased ΔFVCrel (p = 0.04) similarly between sexes (W: Δ 1.6 ± 1.1 vs. M: Δ 2.0 ± 1.6, p = 0.78). DB was also found to be similar between the sexes (p = 0.85). Conclusion These data clearly indicate women produce a greater exercise vasodilator response. Furthermore, contrary to experiments in animal models, these data are the first to demonstrate vascular control by NOS and COX is similar between sexes.

Potentiation of the NO-cGMP pathway and blood flow responses during dynamic exercise in healthy humans

“…Third, data were collected across three separate research cohorts in both men and women, thus limiting our ability to control for inter-subject variability. However, we have shown previously that the role of NO in exercise hyperemia is unlikely to be sex-dependent (Kellawan et al 2015). In addition, the method of signal processing differed between protocols – resulting in lower absolute blood flow values in Protocol 2.…”

“…Both sildenafil and L-NMMA have half-lives >1 hour (Mayer et al 1999; Nichols et al 2002); which prohibit our ability to adequately study each independent condition in the same individuals on a single study day. Data from subjects in Protocol 2 were published previously (Harrell et al 2015; Kellawan et al 2015). …”

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

“…Forearm blood flow (artery diameter, blood velocity) was measured using Doppler ultrasound (Vivid 7; General Electric, Milwaukee, WI) with the subject supine using methods published previously (21,24,33). With the use of technology developed by Herr et al (18), the Doppler audio information from the ultrasound was converted into a real-time digital flow velocity signal using fast Fourier transform (18).…”

“…Isoproterenol (isoproterenol hydrochloride injection; Marathon Pharmaceuticals) was infused at four separate doses (1,3,6, and 12 ng·100 g Ϫ1 ·min Ϫ1 ), similar to those published previously (10,11,17). N G -monomethyl-L-arginine (L-NMMA; acetate; Clinalfa BaChem) was infused at a rate of 10 mg/min over 5 min, followed by a 1 mg/min maintenance dose (5,7,21). Ketorolac (ketorolac tromethamine; Wockhardt) was infused at a rate of 1.2 mg/min for 5 min, followed by a 0.1 mg/min maintenance dose (7,21).…”

“…N G -monomethyl-L-arginine (L-NMMA; acetate; Clinalfa BaChem) was infused at a rate of 10 mg/min over 5 min, followed by a 1 mg/min maintenance dose (5,7,21). Ketorolac (ketorolac tromethamine; Wockhardt) was infused at a rate of 1.2 mg/min for 5 min, followed by a 0.1 mg/min maintenance dose (7,21).…”