Calcium channel blockade in rats with cyclosporine-induced vasoconstriction.
Calcium channel blockade has been found to attenuate nephrotoxicity of cyclosporine. However, it is not known whether intrarenal vasoconstriction caused by cyclosporine is totally mediated by vascular smooth muscle calcium influx. To study the protective effects of two calcium blockers on cyclosporine-induced intrarenal vasoconstriction and renal microvascular blood flow, hydronephrotic rat kidneys were suspended in an environmentally controlled tissue bath. Renal microvessel diameters and microvascular blood flow were determined by in vivo videomicroscopy and Doppler velocimetry. Calcium channel blockade was achieved by adding verapamil hydrochloride (5.6 x 10(-5) M) or diltiazem hydrochloride (2.8 x 10(-5) M) to the tissue bath, which respectively resulted in a 15 +/- 2% and 16 +/- 3% interlobular arteriolar dilation, a 13 +/- 3% and 12 +/- 2% afferent arteriolar dilation, and a 60 +/- 8% and 46 +/- 14% increase in interlobular blood flow. When cyclosporine (1.7 x 10(-3) M) was added to the tissue bath, there was a constriction of the interlobular arterioles to 4 +/- 3% below baseline in rats receiving verapamil and 9 +/- 3% below baseline in rats receiving diltiazem. Microvascular blood flow was reduced by the addition of cyclosporine to 3 +/- 4% above original baseline values in the verapamil group and 22 +/- 6% below baseline in the diltiazem group. Afferent arterioles were similarly constricted by cyclosporine. The results indicate that calcium blockade causes preglomerular vasodilation and protects the microvascular blood flow induced by cyclosporine. Since verapamil or diltiazem did not prevent arteriolar constriction as observed when cyclosporine was added, it was concluded that the mechanism of acute cyclosporine-induced vasoconstriction is not solely mediated by vascular smooth muscle calcium influx through potential dependent channels.
Abraham
J S
JS
Department of Surgery, University of Louisville School of Medicine, Louisville 40292.
Bentley
F R
FR
Garrison
R N
RN
D000818:Animals; D016572:Cyclosporine / Q000037:antagonists & inhibitors*; D004110:Diltiazem / Q000494:pharmacology*; D004195:Disease Models, Animal; D006869:Hydronephrosis / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D016572:Cyclosporine; D014700:Verapamil; D004110:Diltiazem