Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation

Abstract

Device-based therapy for resistant hypertension by electrical activation of the carotid baroreflex is currently undergoing active clinical investigation, and initial findings from clinical trials have been published. The purpose of this mini-review is to summarize the experimental studies that have provided a conceptual understanding of the mechanisms that account for the long-term lowering of arterial pressure with baroreflex activation. The well established mechanisms mediating the role of the baroreflex in short-term regulation of arterial pressure by rapid changes in peripheral resistance and cardiac function are often extended to long-term pressure control, and the more sluggish actions of the baroreflex on renal excretory function are often not taken into consideration. However, because clinical, experimental, and theoretical evidence indicates that the kidneys play a dominant role in long-term control of arterial pressure, this review focuses on the mechanisms that link baroreflex-mediated reductions in central sympathetic outflow with increases in renal excretory function that lead to sustained reductions in arterial pressure.

Fig. 1.

Changes in mean arterial pressure and heart rate during chronic baroreflex activation (n = 6). Values are means ± SE. [Borrowed with permission from (21).].

Fig. 2.

Changes in mean arterial pressure and sodium excretion before and after induction of ANG II hypertension. Values are means ± SE (n = 6). P < 0.05 vs. control [Borrowed with permission from (17).].

Fig. 3.

Hemodynamic, renal excretory, and neurohormonal responses to 1 wk of carotid baroreflex activation: comparison between experimental data [bars redrawn with permission from (23)] and QHP2008 simulation (line). MAP, mean arterial pressure; HR, heart rate: U_NaV, urinary sodium excretion; NE, plasma norepinephrine concentration; PRA, plasma renin activity. [Borrowed with permission from (12).].

Fig. 4.

Changes in mean arterial pressure and heart rate during chronic baroreflex activation in dogs with obesity-induced hypertension (n = 6). Values are means ± SE. *P < 0.05 vs. day 32. Lean control values (open bars) are also presented as reference. [Borrowed with permission from (22).].