Natriuretic response to renal medullary endothelin B receptor activation is blunted in chronic angiotensin II‐infused rats

Abstract

Endothelin B (ETB) receptors, highly expressed in the renal medulla, function to promote sodium and water excretion such that the impairment of ETB receptor function results in salt‐dependent hypertension. Since chronic angiotensin (Ang) II also results in salt‐dependent hypertension, we hypothesized that renal medullary ETB receptor function is impaired in Ang II‐dependent hypertension. We compared the diuretic and natriuretic response to intramedullary infusion of ETB receptor agonist sarafotoxin 6c (S6c) in rats treated with Ang II (65 ng/min s.c.) or vehicle for 14 days. Rats were anesthetized and renal perfusion pressure maintained at a normotensive level in Ang II rats via an adjustable clamp placed around aorta. Urine was collected during 2 consecutive 20 min periods for baseline collection followed by 4 additional 20 min periods of intramedullary saline or S6c (0.45 μg/kg/h) infusion. Renal medullary blood flow (MBF) was determined by laser‐doppler flowmetry. In the vehicle group, S6c significantly increased urine flow (Δ8.4+1.7 μL/min; p<0.01) and sodium excretion (Δ0.79+0.24 μmol/min; p<0.01). However, Ang II rats did not display an increase of urine flow (Δ0.7+0.7 μL/min) and sodium excretion (Δ‐0.06+0.04 μmol/min) during S6c infusion. S6c did not affect MBF in either group. These data demonstrate that renal medullary ETB receptor function is impaired in Ang II‐dependent hypertension.