Estrogen, Exercise Training, and Nitric Oxide-Mediated Sympatholysis
Creators: Collison, Breanne
Publisher: name: University of Alberta Library
Year: 2022

<p>Contraction-mediated inhibition of sympathetic vasoconstriction (sympatholysis) is enhanced in female compared with male rats. Acute pharmacological blockade of nitric oxide (NO) production abolished the sex difference in sympatholysis, indicating that NO-mediated sympatholysis is elevated in female rats. Estrogen has been shown to upregulate expression of the enzyme nitric oxide synthase (NOS), suggesting that estrogen may be an important regulator of NO bioavailability. Indeed, sympatholysis is impaired in estrogen-deficient rodents and humans, and estrogen supplementation appears to restore sympatholysis. NOS is expressed in neuronal (nNOS), endothelial (eNOS), and inducible (iNOS) isoforms and NO derived from eNOS and nNOS has been shown to inhibit vasoconstriction in resting and contracting skeletal muscle in male rats. Moreover, skeletal muscle nNOS expression and nNOS-mediated sympatholysis were enhanced following exercise training in male rats, suggesting that physical activity may modulate NO bioavailability. The reduced sympatholysis reported in estrogen- deficient rats and humans may be due to impaired nNOS function, though the effect of estrogen bioavailability on NOS isoform-specific mediated inhibition of sympathetic vasoconstriction has yet to be investigated. Further, no studies have examined whether exercise training can restore NO-mediated sympatholysis in estrogen-deficient female rats. Therefore, the purpose of this study was to investigate the role of estrogen in NOS isoform-specific mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of sedentary and exercise-trained female rats. I hypothesized that: 1) sympatholysis would be blunted in sedentary estrogen-deficient rats relative to sedentary control rats; 2) exercise training would increase sympatholysis in estrogen-deficient rats, but not control rats; and 3) the effect of exercise training would be nNOS-dependent. Eight week-old female Sprague-Dawley rats were familiarized to exercise on a motorized treadmill, then randomly assigned to sedentary ovary- intact (SOI, n=10), sedentary ovariectomized (SOVX, n=9), exercise-trained (10 weeks, 5 days/week, 600m, 40m·min-1, 5% grade) ovary-intact (TOI, n=13), or exercise-trained ovariectomized (TOVX, n=10) groups. Ovariectomy group rats were then anesthetized, and both ovaries surgically removed. Following sedentary behavior or exercise training, all rats were anesthetized and instrumented for measurement of blood pressure and leg blood flow (LBF). Blood pressure was measured at the right carotid artery and mean arterial pressure (MAP) was calculated. LBF was measured at the right femoral artery, and femoral vascular conductance (FVC) was calculated as FVC=LBFMAP. The sciatic nerve and lumbar sympathetic chain were fitted with stimulating electrodes, and the left femoral vein was cannulated for drug delivery. Vasoconstriction in response to stimulation of the lumbar sympathetic chain at 2 Hz and 5 Hz was assessed at rest and during muscle contraction at 60% of maximal contraction force. The effect of exercise training, estrogen status, and NO on sympathetic vasoconstrictor responsiveness (% change in FVC) and sympatholysis was assessed by two-way repeated measures (group x drug condition) ANOVA. Resting sympathetic vasoconstrictor responsiveness was not different following selective nNOS blockade (p&gt;0.05), but was increased (p0.05) in the presence of selective nNOS inhibition, but was increased (p0.05) between groups or drug conditions. At 5 Hz, sympatholysis was blunted (p0.05) following exercise training. In conclusion, sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle was not dependent on estrogen bioavailability. Additionally, NO derived from eNOS appears to inhibit sympathetic vasoconstriction at rest and during muscle contraction, whereas NO derived from both eNOS and nNOS are important during high frequency stimulation during muscle contraction, regardless of estrogen bioavailability. Finally, exercise training did not alter sympathetic vasoconstrictor responsiveness and sympatholysis regardless of estrogen bioavailability.</p>