Villarraga, Nicolas

Respiratory muscle dysfunction is thought to contribute to exercise intolerance in heart failure with preserved ejection fraction (HFpEF); however, the underlying mechanisms are unknown. In the present study, patients with HFpEF had greater increases in leg muscle vascular resistance index and greater decreases in leg muscle blood flow index compared with controls during inspiratory resistive breathing (to activate the metaboreflex). Furthermore, respiratory muscle blood flow index responses normalized to pressure generation during inspiratory resistive breathing were exaggerated in HFpEF compared with controls.

Introduction Peripheral nervous system feedback arising from mechanically and metabolically sensitive afferents (Group III/IV, respectively) are central components of the exercise pressor reflex. Experimentally, locomotor venous distention can be simulated via subsytolic regional circulatory occlusion (SubRCO) thereby augmenting the exercise pressor reflex. Furthermore, high pedal frequency increases type II muscle fiber recruitment during exercise likely increasing non‐oxidative metabolism. To date, studies investigating the influence of aging on the exercise pressor reflex have presented conflicting data with most utilizing small muscle mass exercise (e.g. handgrip). Therefore, the purpose of this study was to determine the influence of SubRCO, pedal frequency, and the combination thereof on blood pressure (BP) during exercise in older and younger adults. We hypothesized that during exercise 1) independent of pedal frequencies and age, SubRCO will augment BP and 2) older adults will have greater increases in BP at high pedal frequencies with and without SubRCO compared younger adults. Methods 10 younger (22±2 yrs; 4M/6W; 24±4 kg/m 2 ) and 10 older (63±10yrs; 4M/6W; 24±4 kg/m 2 ) adults participated in two study visits each consisting of two cycling exercise sessions at 20 W, with bilateral upper thigh pressure cuffs. Participants engaged in 3 minutes of exercise at 35 (LOW) or 100 (HIGH) rpm with 5 additional minutes of exercise at that rpm with no cuffing (CTL) or SubRCO in randomized order. Systolic and diastolic blood pressure (SBP and DBP, respectively) were measured via manual sphygmomanometry. Mean arterial pressure (MAP) was calculated as (SBP‐DBP)/3+DBP and the changes in MAP from rest are reported. Results During LOW, SubRCO resulted in greater MAP than CTL in younger (CTL: 4±7; SubRCO: 13±7 mmHg) and older adults (CTL: 4±6; SubRCO: 13±4 mmHg) (both p<0.01). During HIGH, SubRCO resulted in greater MAP than CTL in younger (CTL: 7±4; SubRCO: 20±6 mmHg) and older adults (CTL: 20±9; SubRCO: 31±8 mmHg) (both p<0.01). Younger and older adults had greater increases in MAP during HIGH CTL and SubRCO compared to LOW CTL and SubRCO, respectively (all, p<0.01). Within LOW, there were no differences between younger and older adults during CTL or SubRCO (all, p>0.05). Within HIGH, older adults had greater increases in MAP than younger adults during CTL and SubRCO (both p<0.01). Conclusion These data support the hypothesis that older compared to younger adults have a greater BP response at higher pedal frequencies during exercise. Our results suggest that aging contributes to a greater exercise pressor response to exercise, possibly due to greater feedback from group III/IV afferents. Support or Funding Information NIH HL126638AHA 18POST3990251 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Introduction The exercise pressor reflex contributes to cardiovascular regulation during exercise. The primary components of the exercise pressor reflex response are the mechanically and metabolically sensitive skeletal muscle afferents (group III and IV, respectively). Experimentally, subsystolic regional circulatory occlusion (SubRCO) leads to venous distention, stimulating primarily group III afferents, thereby augmenting the exercise pressor reflex. Previous studies have reported sex differences in the metaboreflex induced exercise pressor reflex induced cardiovascular responses. Specifically, pre‐menopausal women, compared to age‐matched men, were found to have attenuated cardiovascular responses with mechanoreflex stimulation. However, it is unclear if sex differences are also present in the cardiovascular responses during exercise with locomotor limb venous distention. Therefore, the purpose of this study was to determine the influence of SubRCO during submaximal exercise in men and women. We hypothesized that women will have attenuated increases in mean arterial pressure (MAP) and systemic vascular resistance (SVR) than men during exercise with SubRCO. Methods Twelve men and thirteen women completed two study visits (Age: M: 30±6vs. W: 27±8yrs, p>0.05; BMI: M: 25.4±3.6 vs. W: 22±3 kg/m 2 , p<0.05). The first visit consisted of a peak exercise ergometry test. The second visit consisted of constant‐load cycle ergometry at 30% peak workload with different SubRCO pressures via bilateral upper thigh pressure cuffs. The cuffs remained uninflated (0 mmHg) (CTL) during the first three min of exercise, then were intermittently inflated to 20, 40, 60, 80, or 100 mmHg for two minutes (randomized order). Each inflation period was followed by a 2minute deflation period where the participant continued to exercise. Cardiacoutput (Q) and MAP were measured via continuous hemodynamic photoplethysmography and systemic vascular resistance (SVR) was calculated. Data were reported as delta changes from CTL. Results Compared to 0 mmHg, MAP increased with SubRCO inflation pressures of 60, 80, and 100mmHg in men and women during submaximal exercise (all, p<0.05); however, no differences were present between groups (60 mmHg: M: 6.2±4.2 vs. W: 8.0±5.2; 80mmHg: M: 11.6±5.5 vs. W: 15.1±4.8; 100 mmHg: M: 18.2±6.6 vs. W: 20.5±7.2 mmHg(all, p>0.05)). Similarly, SVR increased with cuff inflation pressures of60, 80, and 100 mmHg compared to 0 mmHg in men and women (p<0.05), while no differences existed between groups (60 mmHg: M: 0.3±0.4 vs W: 0.4±0.5;80 mmHg: M: 0.9±0.5 vs W: 1.1± 0.9; 100 mmHg M: 1.3±0.8vs W: 1.5±0.8mmHg/L/min (all, p>0.05)). In contrast, Q did not change with cuff inflation pressures of 20, 40, 60, 80, or100 mmHg compared to 0 mmHg in men or women during submaximal exercise(p>0.05). Conclusion In contrast to our hypothesis, the MAP and SVR responses were not different between men and women with SubRCO during submaximal exercise. Our findings suggest that sex differences are not present in the cardiovascular response to low‐intensity constant‐load exercise with stimulation of the exercise pressor reflex via lower limb venous distention.

Introduction It is well established that the exercise pressor reflex contributes to cardiovascular control (e.g. mean arterial pressure (MAP)) during exercise. One arm of the exercise pressor reflex includes the metabolically sensitive group IV afferents (i.e. metaboreflex). The metaboreflex‐induced cardiovascular responses to exercise are incompletely understood, especially in women across the aging spectrum. For example, post‐menopausal women have greater increases in MAP and systemic vascular resistance (SVR) during locomotor muscle exercise compared to pre‐menopausal women. However, it is unclear if an exaggerated metaboreflex arising from the locomotor muscles is contributing to these cardiovascular adjustments with exercise in post‐menopausal women. We hypothesized that 1) post‐menopausal women will have an augmented MAP response with isolated metaboreflex activation compared to pre‐menopausal women and 2) the exaggerated increase in MAP in the post‐menopausal women will be primarily due to greater increases in SVR. Methods Pre‐ (n= 10, 25±3yrs, 24±3 kg/m 2 ) and post‐menopausal women (n=12, 58±4yrs, 24±3 kg/m 2 ) performed 2 sessions of cycling exercise at 20 W for 5 min with bilateral upper thigh pressure tourniquets inflated to 90 mmHg. At end exercise, the recovery was randomized to post‐exercise circulatory occlusion (PECO) to isolate the metaboreflex (via bilateral upper thigh pressure tourniquets rapidly inflated to suprasystolic pressure for 2 min) or normal recovery (NR) without intervention. Systolic and diastolic blood pressure were measured via manual sphygmomanometry and MAP was calculated. Cardiac output was measured via open circuit acetylene wash‐in and systemic vascular resistance (SVR) was calculated. Data is reported as the absolute change from rest to recovery. Results MAP was elevated during PECO compared to NR in both groups (p<0.05), while MAP during PECO was greater in post‐ compared to pre‐menopausal women (20±9 vs. 13±5 mmHg, respectively) (p<0.05). Similarly, SVR was elevated during PECO compared to NR in both groups (p<0.05), while SVR was greater during PECO in post‐ compared to pre‐menopausal women (5±3 vs. 3±1 mmHg/L/min, respectively) (p<0.05). In contrast, cardiac output was not different between NR and PECO in either pre‐ (NR: 0.3±1 vs. PECO: −0.2±1 L/min) and post‐menopausal (NR: −0.1±1 vs. PECO: −0.7±0.9 L/min) (all, p>0.05). Conclusion These data demonstrate that isolated metaboreflex stimulation following whole‐body exercise results in exaggerated increases in MAP and SVR in post‐ compared to pre‐menopausal women. These data suggest that exercise pressor reflex‐mediated control of MAP during exercise is accentuated in post‐menopausal women with menopause status.

Reflexes arising from the respiratory and locomotor muscles influence cardiovascular regulation during exercise. However, it is unclear how the respiratory and locomotor muscle reflexes interact when simultaneously stimulated. Herein, we demonstrate that stimulation of the respiratory and locomotor muscle reflexes yielded additive cardiovascular responses during submaximal exercise.