Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex

Abstract

Following sinoaortic denervation, which eliminates arterial baroreceptor input into the brain, there are slowly developing adaptations that abolish initial sympathetic activation and hypertension. In comparison, electrical stimulation of the carotid sinus for 1 wk produces sustained reductions in sympathetic activity and arterial pressure. However, whether compensations occur subsequently to diminish these responses is unclear. Therefore, we determined whether there are important central and/or peripheral adaptations that diminish the sympathoinhibitory and blood pressure-lowering effects of more sustained carotid sinus stimulation. To this end, we measured whole body plasma norepinephrine spillover and alpha(1)-adrenergic vascular reactivity in six dogs over a 3-wk period of baroreflex activation. During the first week of baroreflex activation, there was an approximately 45% decrease in plasma norepinephrine spillover, along with reductions in mean arterial pressure and heart rate of approximately 20 mmHg and 15 beats/min, respectively; additionally, plasma renin activity did not increase. Most importantly, these responses during week 1 were largely sustained throughout the 3 wk of baroreflex activation. Acute pressor responses to alpha-adrenergic stimulation during ganglionic blockade were similar throughout the study, indicating no compensatory increases in adrenergic vascular reactivity. These findings indicate that the sympathoinhibition and lowering of blood pressure and heart rate induced by chronic activation of the carotid baroreflex are not diminished by adaptations in the brain and peripheral circulation. Furthermore, by providing evidence that baroreflexes have long-term effects on sympathetic activity and arterial pressure, they present a perspective that is opposite from studies of sinoaortic denervation.

Fig. 1.

Changes in mean arterial pressure after sinoaortic denervation (SAD; n = 4) and during prolonged baroreflex activation (PBA; n = 6). Values are means ± SE. *P < 0.05 vs. control. Shaded circles indicate end-of-week responses.

Fig. 2.

Changes in heart rate after SAD (n = 4) and during PBA (n = 6). bpm, Beats/min. Values are means ± SE. *P < 0.05 vs. control. Shaded circles indicate end-of-week responses.

Fig. 3.

Changes in whole body plasma norepinephrine spillover (top) and clearance (middle), and plasma norepinephrine concentration (bottom), in response to PBA. Values are means ± SE (n = 6). *P < 0.05 vs. control.

Fig. 4.

Pressor reactivity to the α₁-agonist phenylephrine before, during, and following PBA. Responses were determined following ganglionic blockade. Δ, Change. Values are means ± SE (n = 6). There were no significant differences between any of the dose-response curves.

Fig. 5.

Changes in short-term blood pressure (top) and pulse interval (bottom) variability during PBA. Values are means ± SE (n = 6). *P < 0.05 vs. control.

Fig. 6.

Changes in spontaneous baroreflex sensitivity (top) and in the number of baroreflex (middle) and nonbaroreflex sequences (bottom) during PBA. Baroreflex and nonbaroreflex sequences were normalized per 10,000 heartbeats. Values are means ± SE (n = 6). *P < 0.05 vs. control.