RENAL HEMODYNAMIC-EFFECTS OF CALCIUM-ANTAGONISTS IN RATS WITH REDUCED RENAL MASS

The intrarenal hemodynamic effects of antihypertensive agents vary considerably, and these microcirculatory effects may contribute to long-term structural sequelae in the setting of chronic renal disease. To investigate the consequences of blood pressure reduction with calcium antagonists, 5/6 nephrectomized Munich-Wistar rats underwent baseline determinations of mean arterial pressure, whole kidney function, and single nephron glomerular filtration rate, after which intravenous infusions of verapamil or diltiazem were given in doses that acutely normalized blood pressure; control rats received saline vehicle. During the baseline period, all rats exhibited comparably elevated values for mean arterial pressure and single nephron glomerular filtration rate. During the experimental infusion, control rats exhibited continued single nephron hyperfiltration (84 +/- 8 nl/min) as a result of elevations in both glomerular capillary plasma flow rate (330 +/- 36 nl/min) and glomerular capillary hydraulic pressure (68 +/- 3 mm Hg), whereas the glomerular capillary ultrafiltration coefficient was low [0.050 +/- 0.009 nl/(sec.mm Hg)]. Both verapamil (148 +/- 6 to 103 +/- 3 mm Hg, p < 0.05) and diltiazem (154 +/- 6 to 102 +/- 2 mm Hg, p < 0.05) normalized arterial pressure, which did not change in control rats (150 +/- 7 to 142 +/- 8 mm Hg). Single nephron hyperfiltration and hyperperfusion were comparable among groups during the experimental period; compared with baseline values, diltiazem (97 +/- 8 to 71 +/- 7 nl/min, p < 0.05) but not verapamil (90 +/- 7 to 83 +/- 6 nl/min, p = NS) modestly lowered the single nephron glomerular filtration rate. Compared with vehicle rats, glomerular capillary pressure was reduced in rats receiving verapamil (52 +/- 2 mm Hg) and diltiazem (50 +/- 2 mm Hg), whereas both agents increased the ultrafiltration coefficient [0.102 +/- 0.012 and 0.123 +/- 0.018 nl/(sec.mm Hg), respectively]. Thus, calcium antagonists acutely control glomerular hypertension and improve the ultrafiltration coefficient in remnant kidney rats.