KCl and angiotensin responses in isolated rat renal arterioles: effects of diltiazem and low-calcium medium.
Studies in intact renovascular models have shown that calcium entry blockers inhibit angiotensin (ANG II)-induced vasoconstriction in afferent (AA) but not efferent arterioles (EA), suggesting that increases in smooth muscle cell cytosolic calcium, the initiating intracellular message, result from entry through potential-operated channels in AA, but from organelle storage mobilization or entry through nonpotential-operated channels in EA. The present study examined the effects of diltiazem (10(-5) M) on the constrictor responses to KCl (50 mM) and half-maximal constricting concentrations (EC50) of ANG II and the effects of low-calcium bathing medium on EC50 ANG II responses in isolated rat AA and EA. KCl caused slightly greater decreases in lumen diameter in AA than in EA (P < 0.05) that were completely inhibited by diltiazem in both. Vasoconstriction to ANG II was significantly inhibited by diltiazem (29 +/- 12 vs. 67 +/- 31%; P < 0.02) in AA. However, constrictor response to ANG II in EA was unchanged by diltiazem (42 +/- 32 vs. 41 +/- 31%). Constriction to ANG II of AA in low-calcium medium was significantly attenuated (8 +/- 13 vs. 54 +/- 12%; P < 0.01); however, EA constrictor response was not affected (43 +/- 22 vs. 51 +/- 19%). These data indicate that EC50 ANG II-induced AA constriction requires calcium entry primarily through potential-operated channels. While potential-operated calcium entry channels can be functionally expressed in EA, intracellular calcium mobilization is the primary mechanism for ANG II-induced constriction.
Conger
J D
JD
Department of Medicine, University of Colorado Health Sciences Center, Denver 80220.
Falk
S A
SA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D003470:Culture Media; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D003470:Culture Media; D000804:Angiotensin II; D011189:Potassium Chloride; D004110:Diltiazem; D002118:Calcium