RENAL PROTECTIVE EFFECTS OF EFONIDIPINE IN PARTIALLY NEPHRECTOMIZED SPONTANEOUSLY HYPERTENSIVE RATS

We investigated the effects of a calcium antagonist, efonidipine, whic h was reported to dilate not only afferent arterioles but also efferen t arterioles, on progression of renal failure in salt-loaded partially nephrectomized spontaneously hypertensive rats (SHR). Forty-four SHR' s with 5 of 6 nephrectomy were divided into four groups: group 1 as co ntrol (n=20); group 2, efonidipine-treated (n=8); group 3, enalapril-t reated (n=8); and group 4, nifedipine-treated (n=8). The rats were giv en these drugs and a high-salt diet (5% NaCl) for 8 weeks. During the experiment, systolic blood pressure (SBP) and daily urinary protein ex cretion were measured every 2 weeks. At the end of the study, serum cr eatinine was determined, and renal tissues were obtained for light mic roscopic examination. SEP was markedly reduced by 8-week antihypertens ive treatment. (control, 267+/-7 mmHg; efonidipine, 181+/-7 mmHg; enal april, 200+/-12 mmHg; nifedipine, 184+/-6 mmHg). Glomerular sclerosis developed markedly in the control group, but was partially prevented i n all treated groups. Similarly, urinary protein excretion (UPE) was s uppressed by efonidipine (180+/-16 mg/day) and enalapril (186+/-16 mg/ day vs. 301+/-28 mg/day for control). In contrast, nifedipine failed t o prevent the increase in urinary protein excretion (258+/-22 mg/day). In conclusion, efonidipine attenuates SEP increase and ameliorates gl omerular injury as well as nifedipine and enalapril. Furthermore, bene ficial effects of efonidipine, but not nifedipine, on proteinuria sugg est that different mechanisms mediate the improvement of proteinuria; one possible mechanism could be efferent arteriolar dilation, not repo rted in nifedipine.