Circulatory Effects of Peripheral Chemoreflex Inhibition During Exercise in Treated Hypertension

Abstract

The sensitization of the peripheral (carotid) chemoreflex can cause a sympathetically mediated restraint of blood flow to the exercising muscles in some disease states (e.g., heart failure, COPD). Such impairments in nutritive blood flow have the potential to impair exercise tolerance and raise exercising blood pressure (BP). Increased peripheral chemoreflex sensitivity and pronounced exercise-induced surges in BP have been reported in hypertension. Herein, we tested the hypothesis that suppressing peripheral chemoreflex sensitivity improves skeletal muscle blood flow during exercise in hypertension. Fourteen patients with treated hypertension (age 69±11 years, systolic BP 136±12 mmHg, diastolic BP 80±11 mmHg; mean ± SD) performed a resting baseline (3 min), an isocapnic hypoxia rebreathing test and rhythmic handgrip exercise (3 min at 50% of maximal voluntary contraction, 1 s contraction and 2 s relaxation) with either intravenous 0.9% saline (control) or low-dose dopamine (2 mcg·kg−1·min−1) to inhibit the peripheral chemoreflex. BP (finger plethysmography), heart rate (HR; electrocardiogram) and ventilation (V̇E; heated pneumotachometer) were recorded throughout. Brachial artery blood flow was monitored (duplex Doppler ultrasound) at rest (1 min average) and during handgrip (15 s averages), and vascular conductance calculated as brachial blood flow/mean BP. Dopamine blunted the peak (last 15 s) increase in V̇E during isocapnic hypoxic rebreathing compared to saline infusion (Δ6±6 vs. Δ9±5 L·min−1, P=0.026), while also attenuating peak mean BP (Δ3±4 vs. Δ8±6 mmHg, P=0.007). Dopamine did not change resting mean BP (95±10 vs. 98±10 mmHg, P=0.155) and HR (68±7 vs. 66±8 beats·min−1, P=0.100). However, dopamine increased resting brachial blood flow (59±20 vs. 48±16 mL·min−1, P=0.030) and vascular conductance (0.565±0.246 vs. 0.483±0.160 mL·min−1·mmHg−1, P=0.039) and decreased resting V̇E (10.5±3.2 vs. 11.5±3.1 L·min−1, P=0.036) versus saline. Handgrip increased brachial artery blood flow (p<0.05 vs. rest after 45 s), vascular conductance (p<0.05 vs. rest after 45 s) in both saline and dopamine trials, while mean BP, HR and V̇E were unchanged (main effect of time P=0.829, P=0.954 and P=0.255, respectively). Notably, brachial artery blood flow (e.g., Δ76±54 vs. Δ60±43 mL·min−1 at 60 s) and vascular conductance (e.g., Δ0.730±0.440 vs. Δ0.570±0.424 mL·min−1·mmHg−1 at 60 s) responses to handgrip were greater with dopamine than saline (main effect of condition both p<0.0001). Collectively, these findings indicate that the use of low-dose dopamine to suppress peripheral chemoreflex sensitivity improves skeletal muscle blood flow during rhythmic handgrip exercise in patients with treated hypertension. Funding support provided by the Health Research Council of New Zealand (19/687) and the Sidney Taylor Trust. 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.