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1 Department of Physiology, Tulane University School of Medicine, New Orleans, LA, USA
2 Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA
* To whom correspondence should be addressed. E-mail: navar{at}tulane.edu.
L-type Ca2+ channels predominantly influence pre-glomerular arterioles, but there is less information regarding the role of T-type Ca2+ channels in regulating the renal microvasculature. We compared the effects of T and L-type channel blockade on afferent and efferent arterioles using the in vitro blood-perfused juxtamedullary nephron preparation. Single afferent or efferent arterioles of Sprague-Dawley rats were visualized and superfused with solutions containing Ca2+ channel blockers. We confirmed that L-type channel blockade with diltiazem dilates afferent arterioles, but has no significant effects on efferent arterioles. In contrast, T-type channel blockade with pimozide (10µmol/L) or mibefradil (1µmol/L) dilated both afferent (26.8±3.4%, 24.6±1.9%) and efferent (19.2±2.9%, 19.1±4.8%) arterioles. Adding diltiazem did not significantly augment the dilation of afferent arterioles elicited by pimozide and mibefradil, and adding pimozide after diltiazem likewise did not elicit further vasodilation. Diltiazem blocked the depolarization-induced afferent arteriolar constriction elicited by 55mM KCl; however the constrictor response to KCl remains intact during treatment with 10µM pimozide. Pimozide also prevented the afferent arterioles from exhibiting autoregulatory mediated constrictor responses to increases in perfusion pressure. We conclude that T-type channel blockers dilate efferent arterioles as well as afferent arterioles and diminish afferent arteriolar autoregulatory responses to changes in perfusion pressure. To the extent that these agents exert their effects primarily on T-type Ca2+ channels in our experimental setting, these results indicate that T-type channels are functionally expressed in juxtamedullary afferent and efferent arterioles and may act cooperatively with L-type channels to regulate afferent arteriolar resistance. Because L-type channels are not functionally expressed in efferent arterioles, T-type channels may be particularly significant in the regulation of efferent arteriolar function.
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