Blockade of T‐type calcium channel with R(−) efonidipine ameliorates the renal ischemia induced by angiotensin II in Sprague‐Dawley rats

Abstract

Blockade of T‐type calcium channel (TCC) has been shown to protect from renal injury. We have previously demonstrated ‐that blockade of TCC with R(−) efonidipine (R(−)EFO), a specific TCC blocker, could selectively increase renal medullary blood flow (MBF) in Sprague‐Dawley (SD) rats. Present study was designed to determine whether blockade of TCC with R(−)EFO would ameliorate the renal medullary ischemia induced by angiotensin II (AngII) in SD rats. Renal cortical blood flow (CBF) and MBF were simultaneously monitored by laser‐Doppler flowmetry in anesthetized SD rats. Following 30 min. baseline, AngII was intravenously infused for 30 min (50 ng/kg/min), and then R(−)EFO (0.25mg/h, intravenously) was infused together for 90 min and compared to the vehicle group. Urine was collected for hydrogen peroxide excretion (UH2O2V) measurement. Infusion of AngII significantly reduced renal CBF and MBF by 22±3.4% and 28±1.7% (P<0.05), respectively. However, the reduction of MBF was significantly attenuated by R(−)EFO (P<0.05). No significant change was observed in CBF between the two groups. Moreover, R(−)EFO significantly attenuated the increase in UH2O2V induced by AngII (P<0.05). We conclude that blockade of TCC with R(−)EFO would attenuate AngII‐induced reductions in renal MBF by altering AngII‐induced renal oxidative stress. Supported by the Grants‐in‐Aid from the Min. of ECSST of Japan (No. 17590181)