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(Hypertension. 2003;41:1359.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Functional Role of ET_B Receptors in the Renal Medulla

From the Vascular Biology Center, Departments of Surgery, Physiology, and Pharmacology and Toxicology, Medical College of Georgia, Augusta.

Correspondence to David M. Pollock, PhD, Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd, Augusta, GA 30912-2500. E-mail dpollock{at}mail.mcg.edu

Experiments were conducted to determine the influence of ET_B receptors in the control of renal medullary function. The acute relation between renal perfusion pressure (RPP) and natriuresis was examined in anesthetized rats treated with the ET_B antagonist A-192621 (10 mg/kg IV). In A-192621–treated rats, sodium excretion (UNaV) was 0.4±0.1, 0.6±0.3, and 2.7±0.5 µmol/min at RPP of 80±1, 107±1, and 144±5 mm Hg, respectively. In control rats, UNaV averaged 0.8±0.4, 3.4±1.2, and 8.1±1.7 µmol/min at RPP of 77±2, 115±5, and 137±3 mm Hg, respectively. For normal and high RPP, UNaV was significantly lower in A-192621–treated rats compared with control rats. Additional experiments determined the effects of Big ET-1 (10 pmol/kg per minute) on intrarenal blood flow. Medullary blood flow (MBF) and cortical blood flow were measured in anesthetized rats by single-fiber, laser Doppler flowmetry. Cortical blood flow significantly decreased in response to Big ET-1 in rats on a normal or high salt diet. Big ET-1 significantly increased MBF in rats on a high salt diet, whereas there was no change in MBF in rats on a normal salt diet. These results demonstrate that medullary vasodilation produced by Big ET-1 is more prominent in rats on a high salt diet and are consistent with a contribution of ET_B-mediated events in the natriuretic response to high salt intake. Taken together, these findings support the hypothesis that endothelin plays an important role in regulating sodium excretion through activation of ET_B receptors.

Key Words: endothelin • receptors, endothelin • natriuresis • blood flow

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