Endothelin in Renal Physiology and Disease

Editor(s): Barton M. (Zürich) 
Kohan D.E. (Salt Lake City, Utah) 
Table of Contents
Vol. 172, 2011
Section title: Molecular Biology and Physiology of Endothelin in the Kidney

Endothelin in the Control of Renal Sympathetic Nerve Activity

Kopp U.C.
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The kidney is densely innervated by sympathetic nerves. Increases in renal sympathetic nerve activity (RSNA) decrease urinary sodium excretion. The kidney also has abundant afferent sensory innervation, located primarily in the renal pelvic wall. Sympathetic nerve fibers and afferent nerve fibers often run separately but intertwined in the same nerve bundles in the renal pelvic wall, providing anatomic support for a functional interaction between RSNA and afferent renal nerve activity (ARNA). Activation of RSNA increases ARNA, which in turn decreases RSNA by activation of the renorenal reflexes. Thus, RSNA-induced increases in ARNA exert a powerful negative feedback control of RSNA via activation of the renorenal reflexes in the overall goal of maintaining low RSNA to facilitate urinary sodium excretion. A high-sodium diet enhances and a low-sodium diet reduces the RSNA-induced increases in ARNA. The physiologic importance of the dietary-induced changes in the RSNA-mediated increases in ARNA is underlined by salt-sensitive hypertension in rats lacking afferent renal innervation. Endothelin (ET), ETA receptors (R), and ETB-R are present in the renal pelvic wall. ET plays a modulatory role in the activation of the afferent renal nerves that is dependent on dietary sodium intake. In a high-sodium diet, increased activation of ETB-R facilitates the interaction between RSNA and ARNA resulting in suppression of RSNA, via activation of the renorenal reflexes, to limit sodium retention. In a low-sodium diet, increased activation of renal pelvic ETA-R suppresses the interaction between RSNA and ARNA which increases RSNA via impairment of the renorenal reflex mechanism, eventually leading to sodium retention. These findings suggest that the increased renal sympathetic nerve activity and salt-sensitive hypertension in ET-1/ETB-R-deficient subjects is, at least in part, related to suppressed interaction between RSNA and ARNA.

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