Faculty Collaboration Database

L-type calcium channels in the renal microcirculatory response to endothelin. Am J Physiol Renal Physiol 2005 Apr;288(4):F771-7

Date

11/18/2004

Pubmed ID

15547114

DOI

10.1152/ajprenal.00315.2004

Scopus ID

2-s2.0-15044341328 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

The signaling pathways of endothelin (ET)-1-mediated vasoconstriction in the renal circulation have not been elucidated but appear to be distinct between ET(A) and ET(B) receptors. The purpose of this study was to determine the role of L-type Ca(2+) channels in the vasoconstrictor response to ET-1 and the ET(B) receptor agonist sarafotoxin 6c (S6c) in the rat kidney. Renal blood flow (RBF) was measured with an ultrasonic flow probe in anesthetized rats, and a microcatheter was inserted into the renal artery for drug infusion. All rats were given vehicle (0.9% NaCl) or three successive bolus injections (1, 10, and 100 pmol) of ET-1 or S6c at 30-min intervals (n = 6 in each group). ET-1 and S6c produced dose-dependent decreases in RBF. The Ca(2+) channel blocker nifedipine (1.5 mug) significantly attenuated the RBF response only at the highest doses of ET-1 and S6c. In the isolated blood-perfused juxtamedullary nephron preparation, Ca(2+) channel blockade with diltiazem had a very small inhibitory effect on ET-1-induced decreases in afferent arteriolar diameter only at the lowest concentrations of ET-1. In vascular smooth muscle cells isolated from preglomerular vessels, ET-1 produced a typical biphasic Ca(2+) response, whereas S6c had no effect on cytosolic Ca(2+). Furthermore, Ca(2+) channel blockade (diltiazem or Ni(2+)) had no effect on the peak or sustained increase in cytosolic Ca(2+) produced by ET-1. These results support the hypothesis that L-type Ca(2+) channels play only a minor role in the constrictor responses to ET-1 in the renal microcirculation.

Author List

Pollock DM, Jenkins JM, Cook AK, Imig JD, Inscho EW

MESH terms used to index this publication - Major topics in bold

Animals
Arterioles
Blood Pressure
Calcium Channels, L-Type
Endothelin-1
Juxtaglomerular Apparatus
Male
Muscle, Smooth, Vascular
Nephrons
Rats
Rats, Sprague-Dawley
Renal Circulation
Vasoconstriction