Attenuated vasoconstrictor responses to endothelin in afferent arterioles during a high-salt diet

Abstract

Endothelin-1 (ET-1) is increased in rats on a high-salt (HS) diet and participates in salt-dependent hypertension. Afferent arterioles (AA) are important for long-term blood pressure control, and therefore we hypothesized that a HS diet would alter their responsiveness to ET-1. Sprague-Dawley rats were fed either a normal-salt (NS; 0.66% NaCl) or HS (8%) diet for 1 wk. Diameters of AA were determined in response to increasing concentrations of big ET-1, ET-1, sarafotoxin 6c (S6c), or norepinephrine (NE), using the blood-perfused juxtamedullary nephron technique. ET-1 responses were also determined during blockade of endothelin type A (ETA) or type B (ETB) receptors with 10 nM ABT-627 or 30 nM A-192621, respectively. Expression of ETA and ETB receptors was determined in renal microvessels. Responses of AA to big ET-1, ET-1, and S6c were significantly attenuated during a HS diet (e.g., response to 10−10 M ET-1 in NS vs. HS rats: −52.5 ± 10.2 vs. +5.6 ± 11.3% of control diameter; P < 0.05), with no change in the responses to NE. ETB, but not ETA receptor blockade abolished the different response to ET-1 between the NS and HS groups. ETB receptor expression in renal microvessels was increased in response to HS (17.7 ± 2.4 vs. 6.6 ± 3.0% of β-actin, P = 0.02), whereas ETA receptor expression was unchanged. These results suggest that the reduced vasoconstrictor response of AA to endothelin peptides during a HS diet is mediated by increased vasodilatory function of endothelial ETB receptors. By preserving renal blood flow, this may be an important mechanism to restore sodium balance during a HS diet.