EFFECTS OF THE NOVEL MULTIPLE-ACTION AGENT CARVEDILOL ON SEVERE NEPHROSCLEROSIS IN RENAL ABLATED RATS

Antihypertensive drugs have differing effects on renal hemodynamics an d morphology. We analyzed whether the use of a new beta adrenoceptor a ntagonist and vasodilator, carvedilol (CVD), slows the progression of nephrosclerosis and whether the renoprotective effect as well as reduc tion in cardiac hypertrophy is dependent on the degree of blood pressu re reduction. Fifty-four adult male Sprague-Dawley rats were distribut ed among five groups: group I served as untreated controls with 5/6 ne phrectomy (Nx); group II, sham (no renal ablation or drug treatment); group III, CVD 5 (5/6 Nx and treatment with oral CVD at 5 mg/kg/day); group IV, CVD 10 (5/6 Nx and treatment with oral CVD at 10 mg/kg/day); and group V, CVD 20 (5/6 Nx and treatment with oral CVD at 20 mg/kg/d ay). Tail-cuff blood pressure and 24-hr urine samples were obtained be fore and at 3, 5 and II weeks of treatment with CVD. At the end of the study period, blood was taken to measure serum creatinine, plasma ren in activity and CVD levels, as well as the remnant kidney and heart fo r morphological studies. There was a significant reduction in 24-hr U- ProtV in all the CVD-treated groups, and it was increasingly evident w ith the highest dose used. However, only rats receiving doses of 10 an d 20 mg/kg/day of CVD exhibited significant decreases in blood pressur e. Elevated serum creatinine levels seen in untreated controls were si gnificantly decreased by CVD in treated rats (P < .01), indicating tha t. glomerular filtration rate was improved by this drug. This was asso ciated with a significant increase in U-NaV. Concomitant and significa nt (P < .01) decreases in plasma renin activity were observed in sham and CVD-treated rats. CVD-treated animals had considerably reduced ren al damage (P < .01) and cardiac hypertrophy (P < .01) compared with un treated controls. These data indicate that CVD is effective in delayin g progression of renal damage and provides beneficial effects in the r emnant kidney and cardiac hypertrophy, even at nonhypotensive doses.