CHRONIC CARVEDILOL REDUCES MORTALITY AND RENAL DAMAGE IN HYPERTENSIVESTROKE-PRONE RATS

The effects of carvedilol, a novel vasodilating beta-blocker and antio xidant, and propranolol on survival, neurobehavioral deficits, cardiov ascular parameters, plasma renin, plasma aldosterone levels and renal pathology were determined in stroke-prone spontaneously hypertensive r ats. Stroke-prone spontaneously hypertensive rats were allowed access to 1% NaCl as the drinking solution and a high fat diet supplemented w ith carvedilol (1200 or 2400 ppm) or propranolol (2400 ppm). The contr ol group consisted of stroke-prone spontaneously hypertensive rats pla ced on the same diet with no drug supplement. Animals fed propranolol had a blood level of 864 +/- 68 ng/ml, whereas carvedilol-fed animals had blood levels of 24 +/- 4 ng/ml at 1200 ppm and 471 +/- 145 ng/ml a t 2400 ppm. Carvedilol and propranolol treatment resulted in significa nt beta adrenoceptor blockade. Both compounds reduced heart rate, but had no significant effects on systolic arterial blood pressure. Carved ilol- and propranolol-treated animals also exhibited significant, prol onged protection from neurobehavioral deficits and mortality (P < .01) . Elevated plasma renin activity and aldosterone levels seen in untrea ted controls were significantly decreased by propranolol (P < .05), an d to a considerably greater extent by the same dose of carvedilol (P < .01). Carvedilol decreased renal histopathological damage and cardiac hypertrophy to a greater extent (P < .01) than propranolol (at equal doses). Both carvedilol (P < .01)- and propranolol (P < .01)-treated a nimals had considerably reduced renal damage at 18 weeks of treatment. Carvedilol reduced renal damage more than propranolol (P < .05). In a ddition, the lower (1200 ppm) dose of carvedilol, which decreased neur obehavioral deficits and mortality, had no significant effects on orga n mass or renal function, but significantly (P < .01) reduced renal da mage. These data indicate that both beta adrenoceptor blockers, especi ally carvedilol to a considerably greater degree, convey significant p rotection in a genetic model of severe hypertension that results in re nal and cardiovascular organ pathology, neurobehavioral deficits and p remature death.