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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Effects of Calcium Channel Blockade on Angiotensin II-Induced Peritubular Ischemia in Rats

Second Department of Internal Medicine (N.K., H.K., G.-P.S., M.R., H.H., K.M., T.H., M.K.), Life Science Research Center (A.M.), and Department of Pharmacology (M.R., S.K., Y.A., A.N.), Kagawa University Medical School, Kagawa, Japan; and Department of Urology, Nagoya University School of Medicine (T.Y.), Nagoya, Japan

Recent studies have indicated that derangement of peritubular capillary (PTC) circulation with consequent tubulointerstitial hypoxia plays a pivotal role in the pathogenesis of renal injury. The present study was performed to determine whether azelnidipine, a new dihydropyridine calcium channel blocker, attenuates angiotensin II (AngII)-induced peritubular ischemia in anesthetized rats. The superficial PTCs were visualized directly using an intravital fluorescence videomicroscope system, and the PTC blood flow was evaluated by analyzing the velocity of fluorescein isothiocyanate-labeled erythrocytes. Intravenous infusion of AngII (50 ng/kg/min, 10 min) significantly increased mean arterial pressure (MAP) and renal vascular resistance (RVR) (by 35 ± 3% and 110 ± 32%, respectively), and decreased total renal blood flow (RBF) and PTC erythrocyte velocity (by –34 ± 4 and –37 ± 1%, respectively). Treatment with azelnidipine (5 µg/kg/min i.v., 10 min) had no effect on basal MAP, RBF, RVR, or PTC erythrocyte velocity. However, azelnidipine markedly attenuated the AngII-induced increases in MAP (7 ± 3%) and RVR (40 ± 4%) and decreases in RBF (–24 ± 1%) and PTC erythrocyte velocity (–22 ± 1%). Similar attenuation in the AngII-induced responses of MAP, RBF, RVR, and PTC erythrocyte velocity were observed in rats treated with a higher dose of azelnidipine (20 µg/kg/min i.v., 10 min), which significantly decreased basal MAP and RVR and increased RBF and PTC erythrocyte velocity. These data suggest that calcium channel blockade attenuates AngII-induced peritubular ischemia, which may be involved in its beneficial effects on renal injury.

Address correspondence to: Dr. Akira Nishiyama, Department of Pharmacology, Kagawa University Medical School, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa 761-0793, Japan. E-mail: akira{at}kms.ac.jp