Effect of long-acting calcium entry blocker (anipamil) on blood pressure, renal function and survival of uremic rats.
To assess more completely the long-term effect of a long-acting calcium channel blocker, anipamil was given p.o. to rats with subtotal (five-sixths) nephrectomy. The mortality rates in anipamil-treated and control groups were 5% and 20%, respectively, at 6 weeks after separation (P less than .01) and 10% and 55%, respectively, at 10 weeks after separation (P less than .01). Mean arterial blood pressure was also more well controlled in the anipamil-treated group (144 +/- 36 vs. 192 +/- 35 mm Hg; n = 20; P less than .05 at week 5). In paired experiments, the degree of renal impairment in the placebo- and anipamil-treated groups, just before the onset of preterminal azotemia, was determined. Rats that were treated with anipamil had lower serum creatinine concentrations, compared with the placebo controls, at 4 to 6 weeks after separation (0.55 +/- 0.02 vs. 0.87 +/- 0.02 mg/100 ml; P less than .05). To dissociate this beneficial effect of anipamil from mean arterial blood pressure control, experiments were also performed to assess the effects of hydralazine on the remnant kidney model of chronic renal failure. Rats with remnant kidneys were divided into three groups and treated with anipamil (2 mg/kg/day), hydralazine (80 mg/liter in drinking water) or control. The anipamil-treated group exhibited significantly greater protection of renal function than did the hydralazine-treated group for the same level of blood pressure control. Thus, a long-acting calcium channel entry blocker such as anipamil may afford an additional cytoprotective effect in the prevention of progression of chronic renal failure beyond the antihypertensive effects of the agent.
Jarusiripipat
C
C
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Chan
L
L
Shapiro
J I
JI
Schrier
R W
RW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006830:Hydralazine / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009392:Nephrectomy; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014511:Uremia / Q000188:drug therapy*
D002121:Calcium Channel Blockers; D011437:Propylamines; D006830:Hydralazine; C045313:anipamil