Maximal aerobic capacity is not correlated with microvascular nitric oxide contribution to endothelium- or beta-2-adrenergic receptor-dependent vasodilation in female adults
Authors: Dillon Gabrielle , Barnes Jill , Limberg Jacqueline , Ranadive Sushant , Baker Sarah , Curry Timothy , Joyner Michael , Harvey Ronée 
Published: May 2023

Background: The menopausal transition is characterized by impairments in microvascular endothelium- and β2-adrenergic receptor (β2AR)-dependent vasodilation, both mediated in part by nitric oxide. Greater aerobic capacity is associated with preserved endothelium-dependent vasodilation in middle-aged and older males, but not estrogen-deficient postmenopausal females. However, the association between aerobic capacity and the nitric oxide contribution to endothelium-dependent vasodilation has not been described in pre- or postmenopausal females. Further, the association between aerobic capacity and β2AR-dependent vasodilation in pre- and postmenopausal females remains elusive. Thus, this study tested the hypothesis that maximal aerobic capacity (V̇O2max) and endothelium- and β2AR-dependent vasodilation (and their respective nitric oxide contributions) would be positively correlated in premenopausal, but not estrogen-deficient postmenopausal females. Methods: Ten premenopausal (PRE, 27±3 yrs) and ten postmenopausal (PM, 59±4 yrs) females participated. V̇O2max was determined by a graded exercise test on a cycle ergometer. Brachial arterial catheters were placed for continuous blood pressure measurement and pharmacologic infusions. Forearm blood flow (FBF) was measured (venous occlusion plethysmography) at baseline (saline infusion) and during infusion of an endothelium-dependent vasodilator (acetylcholine: 1, 2, 4, 8 μg/100mL tissue/min) and β2AR agonist (terbutaline: 0.1, 0.5, 1, 2 μg/100mL tissue/min), both with and without a nitric oxide synthase inhibitor co-infusion (L-NG-monomethylarginine [L-NMMA]: 1 mg/min). Forearm vascular conductance (FVC) was calculated as FBF/mean blood pressure×100. Vasodilation was calculated as the area under the FVC dose response curve (AUC). The nitric oxide contributions were calculated as the difference between the AUC of acetylcholine or terbutaline alone and the AUC of the co-infusion with L-NMMA. Statistical analyses included independent t-tests and linear regression analysis. Results: V̇O2max was not different between groups (PRE: 35.4±8.3 vs. PM: 29.1±7.9 ml/kg/min, p=0.15). Endothelial and β2AR vasodilation were greater in pre- compared to postmenopausal females (endothelial: PRE 45±15 vs. PM 17±13 FVC AUC, p<0.01; β2AR: PRE 35±12 vs. PM 18±11 FVC AUC, p<0.01). V̇O2max was not correlated with endothelium-dependent vasodilation or the nitric oxide contribution of endothelium-dependent vasodilation in pre- or postmenopausal females (r=-0.48-0.06, p>0.05 for all). V̇O2max was not correlated with β2AR-dependent vasodilation or the nitric oxide contribution of β2AR-mediated vasodilation in pre- or postmenopausal females (r=-0.27-0.26, p>0.05 for all). Conclusion: In contrast to what has been previously observed in males, maximal aerobic capacity was not correlated with endothelium- or β2AR-dependent microvascular vasodilation ortheir respective nitric oxide contributions in pre- or postmenopausal females. AHA 14PRE18040000, AHA 898649, NIH DK07352, NIH HL083947, NIH HL118154, NIH HL148144, NCATS UL1 TR000135 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.