L-type calcium channels in the renal microcirculatory response to endothelin.
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.
Pollock
David M
DM
Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500, USA. dpollock@mail.mcg.edu
Jenkins
John M
JM
Cook
Anthony K
AK
Imig
John D
JD
Inscho
Edward W
EW
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D007606:Juxtaglomerular Apparatus / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009399:Nephrons / Q000098:blood supply* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D020746:Calcium Channels, L-Type; D019332:Endothelin-1