Renal responses to chronic suppression of central sympathetic outflow

Abstract

Chronic electric activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure and is currently being evaluated as hypertension therapy for patients with resistant hypertension. However, the chronic changes in renal function associated with natural suppression of sympathetic activity are largely unknown. In normotensive dogs, we investigated the integrative cardiovascular effects of chronic baroreflex activation (2 weeks) alone and in combination with the calcium channel blocker amlodipine, which is commonly used in the treatment of resistant hypertension. During baroreflex activation alone, there were sustained decreases in mean arterial pressure (17±1 mmHg) and plasma (norepinephrine; ≈35%), with no change in plasma renin activity. Despite low pressure, sodium balance was achieved because of decreased tubular reabsorption, because glomerular filtration rate and renal blood flow decreased 10% to 20%. After 2 weeks of amlodipine, arterial pressure was also reduced 17 mmHg, but with substantial increases in norepinephrine and plasma renin activity and no change in glomerular filtration rate. In the presence of amlodipine, baroreflex activation greatly attenuated neurohormonal activation, and pressure decreased even further (by 11±2 mmHg). Moreover, during amlodipine administration, the fall in glomerular filtration rate with baroreflex activation was abolished. These findings suggest that the chronic blood pressure-lowering effects of baroreflex activation are attributed, at least in part, to sustained inhibition of renal sympathetic nerve activity and attendant decreases in sodium reabsorption before the macula densa. Tubuloglomerular feedback constriction of the afferent arterioles may account for reduced glomerular filtration rate, a response abolished by amlodipine, which dilates the preglomerular vasculature.

Figure 1

Mean arterial pressure and heart rate responses to baroreflex activation and amlodipine administration. Values are mean ± SEM (n=6). *P<0.05 versus control.

Figure 2

Continuous 20-hour recordings of mean arterial pressure and renal blood flow during the control and recovery periods and after one and two weeks of baroreflex activation. Values are mean ±SEM (n=4). The grey line superimposed on the RBF data represents the best-fit polynomial equation shared among all datasets.

Figure 3

Changes in mean arterial pressure and heart rate during amlodopine and amlodipine + baroreflex activation. Values are mean ± SEM (n=6). *P<0.05 versus day 7 of amlodopine.