The interactive effects of age and sex on the neuro-cardiovascular responses during fatiguing rhythmic handgrip exercise.

The impact of age on exercise pressor responses is equivocal, likely because of sex-specific neuro-cardiovascular changes with age. However, assessments of the interactive effects of age and sex on muscle sympathetic nerve activity (MSNA) responses to exercise are lacking. We tested the hypothesis that older females would exhibit exaggerated increases in blood pressure (BP) and MSNA discharge patterns during handgrip exercise compared to similarly aged males and young adults. 25 young (25[2] years; mean[SD]) males (YM; n = 12) and females (YF; n = 13), and 23 older (71[5] years) males (OM; n = 11) and females (OF; n = 12) underwent assessments of BP, total peripheral resistance (TPR; modelflow) and MSNA action potential (AP) discharge patterns (microneurography) during incremental rhythmic handgrip exercise and post-exercise circulatory occlusion (PECO). OM demonstrated larger ∆BP and ∆TPR from baseline than YM (both P<0.001) despite smaller increases in ∆APs/burst (OM: 0.4[3] vs. YM: 5[3] spikes/burst, P<0.001), and ∆AP clusters/burst (OM: 0.1[1] vs. YM: 1.8[1] clusters/burst, P<0.001) during exercise. Testosterone was lower in OM versus YM (P<0.001) and was inversely related with ∆BP but positively related with ∆AP clusters/burst in males (both P = 0.03). Conversely, YF and OF demonstrated similar ∆BP and ∆AP discharge during exercise (range: P = 0.75-0.96). Age and sex did not impact hemodynamics or AP discharge during PECO (range: P = 0.08-0.94). Altogether, age-related changes in neuro-cardiovascular reactivity exist in males but not females during fatiguing exercise and seem to be related to testosterone. This sex-specific impact of age underscores the importance of considering biological sex when assessing age-related changes in neuro-cardiovascular control during exercise. KEY POINTS: Older males have the largest increase in blood pressure despite having the smallest increases in sympathetic vasomotor outflow during rhythmic handgrip exercise. Young males demonstrate greater increases in sympathetic action potential (AP) discharge compared to young females during rhythmic handgrip exercise. Older adults (regardless of sex) demonstrate smaller increases in muscle sympathetic nerve activity (MSNA) burst amplitude and total AP clusters compared to young adults during exercise, as well as smaller increases in integrated MSNA burst frequency, incidence and total MSNA activity during post-exercise circulatory occlusion (i.e., independent effect of age). Males, but not females (regardless of age), reflexively modify AP conduction velocity during exercise. Our results indicate that age and sex independently and interactively impact the neural and cardiovascular homeostatic adjustments to fatiguing small muscle mass exercise. Abstract figure legend The effect of age on exercise pressor reflex activation is unclear, likely because of sex-specific neuro-cardiovascular changes with age. While there is some evidence supporting heightened sympathetic activity in older females during exercise, assessments of the interactive effects of age and sex on muscle sympathetic nerve activity (i.e., sympathetic outflow directed toward the skeletal muscle vasculature; MSNA) during exercise are lacking. We tested the hypothesis that older females would exhibit exaggerated increases in blood pressure and MSNA discharge patterns during handgrip exercise compared to similarly aged males and young adults. Using incremental handgrip exercise (One-minute stages at a 50% duty cycle, increasing by 10% maximal voluntary contraction increments) and post-exercise circulatory occlusion, we were able to parse out the central and peripheral determinants of sympathetic discharge. We found age-related reductions in the AP discharge responses, and age-related increases in exercise MAP and TPR observed in males, but not females. Conversely, sympathetic action potential discharge patterns were unaffected during postexercise circulatory occlusion. Altogether, these data highlight the critical importance of considering biological sex in the interpretation of age-related changes in sympathetic neuro-cardiovascular responses to exercise. This article is protected by copyright. All rights reserved.