Hemodynamic And Autonomic Responses To Progressive Metaboreflex Activation In Adults With Hypertension

RATIONALE: The muscle metaboreflex contributes to blood pressure (BP) responses to exercise by increasing cardiac output ([Formula: see text]c) and total peripheral resistance (TPR) via increases in cardiac and vascular sympathetic outflow, respectively. The pressor response to metaboreflex activation is exaggerated in hypertensive adults, but the underlying hemodynamic determinants of the response remain unclear. Adults with hypertension have greater muscle sympathetic neural responses to metaboreflex activation, which may contribute to exaggerated vasoconstriction. We tested the hypothesis that exaggerated TPR responses to a novel progressive metaboreflex activation protocol would contribute primarily to the exaggerated pressor response in hypertensive adults. Methods: 14 normotensive (NTN; 8 females; age: 38±9 y; BMI: 28.0±8.3 kg/m 2 ; 24-h BP: 122/72±6/6 mmHg) and 15 hypertensive (HTN; off-medication; 9 females; age: 43±10 y; BMI: 34.6±7.1 kg/m 2 ; 24-h BP: 143/81±15/9 mmHg) participants performed an ischemic exercise protocol to elicit progressive metaboreflex activation. Under ischemic conditions (BP cuff inflated to 250 mmHg continuously), participants completed three consecutive cycles of 1-min isometric handgrip exercise (20% maximal voluntary contraction [MVC]) followed by 2-min 45-sec of isolated metaboreflex activation (MET1, 2, and 3). We measured BP (finger photoplethysmography), heart rate (HR; 3-lead ECG), stroke volume (SV; Modelflow) and muscle sympathetic nerve activity (MSNA, peroneal nerve, microneurography) to enable calculation of [Formula: see text]c (HR x SV), TPR (mean arterial pressure [MAP] / [Formula: see text]c). Results: MVC was not different between NTN (34±10) and HTN (34±12, P=0.988). Compared to NTN, HTN showed greater increases in MAP (MET1: 3±10 vs. 13±10; MET2: 8±11 vs. 21±13; MET3: 17±12 vs. 30±17 mmHg, P=0.005) and total MSNA (MET1: -81±335 vs. 297±593; MET2: 381±509 vs. 934±1147; MET3: 1152±1006 vs. 2212±1879 a.u., P=0.035) across all stages. No consistent differences were detected between groups in the change in [Formula: see text]c (NTN vs. HTN; MET1: 1.0±0.7 vs. 0.9±1.2; MET2: 1.4±0.9 vs. 1.4±1.7; MET3: 1.5±1.4 vs. 1.5±1.6 L/min, P = 0.923) and TPR (MET1: -2.6±3.8 vs. -0.1±3.4; MET2: -2.3±3.7 vs. -0.1±3.9; MET3: -0.5±4.7 vs. 1.1±4.5 mmHg/L/min, P=0.126). However, patients with HTN had greater HR (MET1: 4±3 vs. 9±6; MET2: 6±4 vs. 12±8; MET3: 5±7 vs. 11±10 bpm, P=0.023), and tended to have lower SV responses (MET1: 9±9 vs. 1±12; MET2: 12±10 vs. 4±15; MET3: 15±12 vs. 7±18 mL, P=0.071), though with greater variability in HTN. Conclusion: Adults with HTN showed greater neural and pressor responses to a novel progressive muscle metaboreflex activation protocol. While NTN and HTN showed similar increases in cardiac output during metaboreflex activation, the rise in [Formula: see text]c was achieved via increases in HR in HTN and increases in SV in NTN controls. These differing mechanisms may have important implications for the development of hypertensive heart disease. NIH R00HL153777 (CMH) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.