Angiotensin II-mediated constriction of afferent and efferent arterioles involves T-type Ca2+ channel activation.
OBJECTIVE
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 micromol/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 micromol/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 micromol/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 micromol/l).


CONCLUSIONS
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.
Feng
Ming-Guo
MG
Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, La. 70112, USA.
Navar
L Gabriel
LG
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology; D004347:Drug Interactions; D007668:Kidney / Q000098:blood supply*; D008297:Male; D010868:Pimozide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010868:Pimozide; D004110:Diltiazem