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

Objective To assess the in-vivo action on the renal microvasculature of the calcium antagonists nifedipine (L-type blocker), efonidipine (L/T-type blo cker), and mibefradil (predominant T-type blocker). Design An intravital ne edle-type charge-coupled device (CCD) camera videomicroscope was introduced to visualize the renal microcirculation directly in vivo. Design An intravital needle-type charge-coupled device (CCD) camera videomi croscope was introduced to visualize the renal microcirculation directly in vivo. Methods In anesthetized mongrel dogs, nifedipine (0.01-1 mg/kg per min), ef onidipine (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 kidne y. Renal microvascular responses to calcium antagonists were directly evalu ated, with concomitant observation of renal clearance. Results Each calcium antagonist caused modest vasodepressor action without affecting heart rate. Nifedipine (1 mg/kg per min, n = 9) increased renal p lasma 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), howeve r, 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 predomin ant (22 +/- 2%) dilatation of afferent arterioles (from 15.5 +/- 0.4 to 18. 9 +/- 0.4 mum, n = 5), compared with that of efferent arterioles (10 +/- 2% ; from 11.0 +/- 0.4 to 12.1 +/- 0.3 mum). 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%). There exists marked heterogeneity in action of nifedipine, efonidipine and mibefradil on the renal microvascular in canine kidneys in vivo. Furthermor e, our current observations suggest an important contribution of T-type cal cium channel activity to efferent arteriolar tone in vivo. (C) 2001 Lippinc ott Williams & Wilkins.