Angiotensin II-mediated constriction of afferent and efferent arterioles involves T-type Ca2+ channel activation

Background/Aims: Previous studies have shown that L-type Ca2+ channel (LCC) blockers prevent the afferent arteriolar ( AA) vasoconstriction elicited by angiotensin II (Ang II), but do not influence its vasoconstrictor effect on efferent arterioles ( EA). The present study tested the hypothesis that Ang II-mediated constriction of AA and EA involves T-type Ca2+ channel (TCC) activation, which may mediate Ca2+ entry responsible for Ang II-induced EA and possibly AA constriction. Methods: Video-microscopic measurements of vascular dimensions were performed on isolated blood-perfused juxtamedullary nephrons from Sprague-Dawley rats. Single AA or EA were visualized and superfused with solutions containing Ang II alone or with a TCC blocker, pimozide, or a LCC blocker, diltiazem. Results: Pimozide at 10 mumol/l significantly dilated EA ( 19.7 +/- 1.4%) as well as AA (24.8 +/- 3.6%). In response to superfusion with Ang II at concentrations of 0.1, 1.0 and 10.0 nmol/l, AA diameter decreased significantly by 15.2 +/- 1.7, 23.3 +/- 3.2 and 36.1 +/- 3.4% and EA diameter also decreased significantly by 11.9 +/- 1.7, 19.6 +/- 2.8 and 31.0 +/- 2.6%, respectively. Pimozide (10 mumol/l) markedly blunted AA (4.6 +/- 1.2, 7.5 +/- 0.6 and 7.9 +/- 1.2%) and EA (2.2 +/- 0.6, 5.4 +/- 1.5 and 7.7 +/- 1.3%) diameter responses to Ang II. Diltiazem ( 10 mumol/l) significantly dilated AA (26.8 +/- 2.2%), and prevented Ang II-mediated constriction of AA. In contrast, diltiazem did not dilate EA (3.3 +/- 0.6%) and failed to inhibit the Ang II-induced EA vasoconstriction; however, the vasoconstriction was reversed by the subsequent addition of pimozide (5 mumol/l). Conclusion: This study provides further functional evidence for TCC channels in the regulation of AA and EA indicating that Ang II-mediated arteriolar constriction may involve activation of TCC in both AA and EA. TCC may play an important role in mediating Ca2+ entry responsible for Ang-induced EA and AA constriction. The role of TCC in mediating Ang II-constrictor actions on EA may be of particular significance because LCC are not normally functional in these vessels. Copyright (C) 2004 S. Karger AG, Basel.