Renal Responses to Chronic Suppression of Central Sympathetic Outflow

Abstract

Chronic electrical 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 mm Hg) and plasma [norepinephrine] (NE, ~35%), with no change in plasma renin activity (PRA). Despite low pressure, sodium balance was achieved due to decreased tubular reabsorption, because GFR and renal blood flow decreased 10–20%. After 2 weeks of amlodipine, arterial pressure was also reduced 17 mm Hg, but with substantial increases in NE and PRA, and no change in GFR. In the presence of amlodipine, baroreflex activation greatly attenuated neurohormonal activation and pressure decreased even further (by 11 ± 2 mm Hg). Moreover, during amlodipine administration the fall in GFR with baroreflex activation was abolished. These findings suggest that the chronic blood pressure lowering effects of baroreflex activation are due, at least in part, to sustained inhibition of renal sympathetic nerve activity and attendant decreases in sodium reabsorption prior to the macula densa. Tubuloglomerular feedback constriction of the afferent arterioles may account for reduced GFR, a response abolished by amlodipine, which dilates the preglomerular vasculature.

Renal Responses to Long-Term Carotid Baroreflex Activation Therapy in Patients With Drug-Resistant Hypertension

“…Iliescu 24 found that baroreflex activation combined with amlodipine resulted in an even greater BP decrease but no change in GFR compared with only baroreflex activation. Our results do not entirely support this observation.…”

“…Iliescu 24 investigated the renal responses to baroreflex activation (for 2 weeks) in 6 normotensive dogs and found, along with a substantial BP reduction, about 10% and 20% decrease in GFR and renal blood flow, respectively, and no change in renal vascular resistance during the activation period. Lohmeier and Iliescu 23,24 explained the decrease in GFR by attenuation of tubular sodium reabsorption attributable to suppression of renal sympathetic nerve activity. This leads to increased sodium chloride delivery to the macula densa, which is expected to result in constriction of afferent arteriole by tubuloglomerular feedback and a concomitant GFR reduction.…”

Sympathetic Nervous System and Hypertension

“…28 Chronic baroreflex activation alone decreased blood pressure, plasma renin activity, and glomerular filtration rate. Amlodipine alone decreased blood pressure and increased plasma renin activity, but glomerular filtration rate was unchanged.…”

Potential Clinical Application of Recently Discovered Brain Mechanisms Involved in Hypertension

“…First, Thrasher 15 produced chronic unloading of arterial baroreceptors in dogs, in which 1 carotid sinus and the aortic depressor nerve were cut, and the carotid sinus from the remaining innervated region was isolated from the systemic arterial pressure. Baroreceptor unloading was then induced by ligating the common carotid artery proximal to the innervated sinus, which led to an increase in arterial pressure that lasted for several weeks; although the initial increase in arterial pressure was not sustained, the level remained above control levels.15 Lohmeier et al 12,13 subsequently observed that electric stimulation of the carotid baroreceptors for 7 days and 2 weeks elicits a sustained reduction in arterial pressure and heart rate associated with a decrease in plasma norepinephrine and renin although the effect may be model dependent and renal nerve independent. In addition to these important observations, a growing body of evidence from recent studies suggests that activation of the sympathetic nervous system has an important role in both the occurrence and the progression of hypertension, as well as target organ damage.…”

“…12,13 In addition, the currently used antihypertensive drugs are suggested to act on the central nervous system.…”