Effect of T-type selective calcium antagonist on renal microcirculation - Studies in the isolated perfused hydronephrotic kidney

Although calcium antagonists exert preferential vasodilation of renal affer ent arterioles, we have recently demonstrated that nilvadipine and efonidip ine, possessing both L-type and T-type calcium channel blocking action, rev erse the angiotensin (Ang) II-induced afferent and efferent arteriolar cons triction. In the present study, we investigated the role of T-type calcium channels in mediating the Ang II-induced efferent arteriolar tone using the selective T-type calcium channel blocker mibefradil. Isolated perfused hyd ronephrotic rat kidneys were used for direct visualization of renal microci rculation. Administration of Ang II (0.3 nmol/L) caused marked constriction of afferent (from 13.5+/-0.6 to 9.2+/-0.6 mum, P<0.01, n=6) and efferent ( from 11.5+/-1.0 to 7.4+/-0.7 <mu>m, P<0.01, n=5) arterioles. Mibefradil (1 <mu>mol/L) dilated both vessels, with 82+/-11% and 72+/-7% reversal of affe rent and efferent arterioles, respectively. Similarly, nickel chloride (100 mu mol/L) caused dilation of both arterioles, similar in magnitude in affe rent (68+/-10%, n=7) and efferent (80+/-7%, n=7) arterioles. To eliminate t he possibility that the mibefradil-induced dilation was mediated by L-type channel blockade, mibefradil was administered in the presence of nifedipine (1 mu mol/L). Thus, nifedipine caused modest efferent arteriolar dilation (30+/-6% reversal, n=9), and subsequent addition of mibefradil elicited fur ther dilation of this vessel (80+/-4%, P<0.01 versus nifedipine). Furthermo re, mibefradil reversed the Ang II-induced efferent arteriolar constriction even in the presence of nifedipine and phentolamine. These findings demons trate that T-type calcium antagonists markedly dilate the Ang II-induced ef ferent arteriolar constriction, but the action is not mediated by inhibitio n of catecholamine release. This potent activity would contribute to the ef ferent arteriolar response to nilvadipine and efonidipine and may offer ben efit in light of glomerular hemodynamics.