Central and peripheral chemoreflexes in humans with treated hypertension

Increased peripheral chemoreflex sensitivity is a pathogenic feature of human hypertension (HTN), while both central and peripheral chemoreflex sensitivities are reportedly augmented in animal models of HTN. Herein, we tested the hypothesis that both central and combined central and peripheral chemoreflex sensitivities are augmented in HTN. Fifteen HTN participants (68 +/- 5 years; mean +/- SD) and 13 normotensives (NT; 65 +/- 6 years) performed two modified rebreathing protocols in which the partial pressure of end-tidal carbon dioxide (P-ETCO2) progressively increased while the partial pressure of end-tidal oxygen was clamped at either 150 mmHg (isoxic hyperoxia; central chemoreflex activation) or 50 mmHg (isoxic hypoxia; combined central and peripheral chemoreflex activation). Ventilation (V-E; pneumotachometer) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded, and ventilatory (V-E vs. P-ETCO2 slope) and sympathetic (MSNA vs. (PETCO2) slope) chemoreflex sensitivities and recruitment thresholds (breakpoint) were calculated. Global cerebral blood flow (gCBF; duplex Doppler) was measured, and the association with chemoreflex responses was examined. Central ventilatory and sympathetic chemoreflex sensitivities were greater in HTN than NT (2.48 +/- 1.33 vs. 1.58 +/- 0.42 L min(-1) mmHg(-1), P = 0.030: 3.32 +/- 1.90 vs. 1.77 +/- 0.62 a.u. mmHg(-1), P = 0.034, respectively), while recruitment thresholds were not different between groups. HTN and NT had similar combined central and peripheral ventilatory and sympathetic chemoreflex sensitivities and recruitment thresholds. A lower gCBF was associated with an earlier recruitment threshold for V-E (R-2 = 0.666, P < 0.0001) and MSNA (R-2 = 0.698, P = 0.004) during isoxic hyperoxic rebreathing. These findings indicate that central ventilatory and sympathetic chemoreflex sensitivities are augmented in human HTN and perhaps suggest that targeting the central chemoreflex may help some forms of HTN. [GRAPHICS] .