Divergent renal vasodilator action of L- and T-type calcium antagonists in vivo

Objective: To assess the in-vivo action on the renal microvasculature of the calcium antagonists nifedipine (L-type blocker), efonidipine (L/T-type blocker), and mibefradil (predominant T-type blocker). Design: An intravital needle-type charge-coupled device (CCD) camera videomicroscope was introduced to visualize the renal microcirculation directly in vivo. Methods: In anesthetized mongrel dogs, nifedipine (0.01-1 mg/kg per min), efonidipine (0.033-0.33 mg/kg per min), or mibefradil (0.01-1 mg/kg per min) was infused intravenously after the insertion of a CCD probe into the kidney. Renal microvascular responses to calcium antagonists were directly evaluated, with concomitant observation of renal clearance. Results: Each calcium antagonist caused modest vasodepressor action without affecting heart rate. Nifedipine (1 mg/kg per rain, n = 9) increased renal plasma flow (RPF) (14 ± 4%, P < 0.05) and glomerular filtration rate (GFR) (19 ± 5%, P < 0.05), and tended to increase the filtration fraction (5 ± 2% increment, P = 0.07). Efonidipine (0.33 mg/kg per min, n = 9), however, had no effect on filtration fraction, with 14 ± 6% increments in RPF (P < 0.05) and 14 ± 7% increments in GFR (P = 0.08). Rather, mibefradil (1 mg/kg per min, n = 9) elicited 6 ± 2% decreases in filtration fraction (P < 0.05), with slight increments in RPF (6 ± 3%) and no changes in GFR. In direct in-vivo microvasculature observations, nifedipine caused predominant (22 ± 2%) dilatation of afferent arterioles (from 15.5 ± 0.4 to 18.9 ± 0.4μm, n = 5), compared with that of efferent arterioles (10 ± 2%; from 11.0 ± 0.4 to 12.1 ± 0.3μm). In contrast, efonidipine caused a similar magnitude of vasodilatation (16 ± 4%) compared with 18 ± 2%; n = 6), and mibefradil caused greater dilatation of efferent arterioles (20 ± 4%, n = 7) than that of afferent arterioles (13 ± 4%). Conclusions: There exists marked heterogeneity in action of nifedipine, efonidipine and mibefradil on the renal microvascular in canine kidneys in vivo. Furthermore, our current observations suggest an important contribution of T-type calcium channel activity to efferent arteriolar tone in vivo.