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

Schneider, M.P., Inscho, E.W. and Pollock, D.M. (2007) Attenuated vasoconstrictor responses to endothelin in afferent arterioles during a high-salt diet. American Journal of Physiology: Renal Physiology, 292(4), F1208-F1214. (doi: 10.​1152/​ajprenal.​00280.​2006)

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 beta-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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Schneider, Dr Markus
• Authors: Schneider, M.P., Inscho, E.W., and Pollock, D.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: American Journal of Physiology: Renal Physiology
• Publisher: American Physiological Society
• ISSN: 1931-857X
• ISSN (Online): 1522-1466
• Published Online: 01 January 2007