Estrogen, Exercise Training, and Nitric-oxide Mediated Sympatholysis
Authors: DeLorey Darren , Collison Breanne , Just Timothy 
Published: May 2024

Our laboratory has previously reported that nitric oxide (NO)-mediated inhibition of sympathetic vasoconstriction in contracting muscle (sympatholysis) was enhanced in female, compared with male rats. Estrogen has been shown to modulate NO synthase (NOS) expression and NO-mediated sympatholysis. Therefore, this study investigated the hypothesis that NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of female rats would be a function of estrogen bioavailability. Further, exercise training has been shown to enhance sympatholysis. Thus, we also investigated the hypothesis that exercise training would restore sympatholysis in estrogen-deficient rats. Female Sprague-Dawley rats were randomized 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. OVX rats had both ovaries surgically removed. Following sedentary behavior or exercise training, rats were anesthetized and instrumented for measurement of blood pressure, femoral vascular conductance (FVC), stimulation of the lumbar sympathetic chain, and contraction of the triceps surae muscle group. The percentage change of FVC (%FVC) in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during muscle contraction (60% maximal contractile force) in control, selective neuronal NOS (nNOS) inhibition (SMTC; 0.6 mg·kg−1 IV), and non-selective NOS inhibition (L-NAME; 10 mg·kg−1 IV) conditions. In the Control condition, sympathetic vasoconstrictor responsiveness (%FVC) in resting and contracting skeletal muscle was not different between groups. Under resting conditions, sympathetic vasoconstrictor responsiveness was not different following selective nNOS inhibition (p>0.05), but was increased (p<0.05, main effect of drug) following non-selective NOS inhibition compared with control and selective nNOS inhibition conditions at both 2 Hz and 5 Hz. During muscle contraction, sympathetic vasoconstrictor responsiveness to 2 Hz sympathetic stimulation was unchanged (p>0.05) in the presence of selective nNOS inhibition, but was increased (p<0.05, main effect of drug) following non-selective NOS inhibition compared with control and selective nNOS inhibition conditions. At 5 Hz, sympathetic vasoconstrictor responsiveness was increased (p<0.05, main effect of drug) by selective nNOS inhibition, and increased further (p<0.05, main effect of drug) by non-selective NOS inhibition. The magnitude of sympatholysis at 2 Hz was not different (p>0.05) between groups or drug conditions. At 5 Hz, sympatholysis was blunted (p<0.05, main effect of drug) in the selective nNOS inhibition condition, and further reduced (p<0.05, main effect of drug condition) following non-selective NOS inhibition in all groups. Sympatholysis was not different (p>0.05) between sedentary and exercise trained groups. In conclusion: 1) sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle was not dependent on estrogen bioavailability; 2) NO blunted vasoconstriction in all groups, however, NO-mediated sympatholysis was not altered by estrogen status, and; 3) exercise training did not alter sympathetic vasoconstrictor responsiveness or sympatholysis regardless of estrogen bioavailability. NSERC, Canada, Canadian Foundation for Innovation. This is the full abstract presented at the American Physiology Summit 2024 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.