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Effects of the novel multiple-action agent carvedilol on severe nephrosclerosis in renal ablated rats
J C Rodriguez-Perez1, A Losada, A Anabitarte
1Research Unit, Hospital Nuestra Señora del Pino, Las Palmas de Gran Canaria, Canary Islands, Spain. jcrodrig@invest.hpino.rcanaria.es
Abstract:
Antihypertensive drugs have differing effects on renal hemodynamics and morphology. We analyzed whether the use of a new beta adrenoceptor antagonist and vasodilator, carvedilol (CVD), slows the progression of nephrosclerosis and whether the renoprotective effect as well as reduction in cardiac hypertrophy is dependent on the degree of blood pressure reduction. Fifty-four adult male Sprague-Dawley rats were distributed among five groups: group I served as untreated controls with 5/6 nephrectomy (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/day). Tail-cuff blood pressure and 24-hr urine samples were obtained before and at 3, 5 and 11 weeks of treatment with CVD. At the end of the study period, blood was taken to measure serum creatinine, plasma renin activity and CVD levels, as well as the remnant kidney and heart for morphological studies. There was a significant reduction in 24-hr U(ProtV) in all the CVD-treated groups, and it was increasingly evident with the highest dose used. However, only rats receiving doses of 10 and 20 mg/kg/day of CVD exhibited significant decreases in blood pressure. Elevated serum creatinine levels seen in untreated controls were significantly decreased by CVD in treated rats (P < .01), indicating that glomerular filtration rate was improved by this drug. This was associated with a significant increase in U(NaV). Concomitant and significant (P < .01) decreases in plasma renin activity were observed in sham and CVD-treated rats. CVD-treated animals had considerably reduced renal damage (P < .01) and cardiac hypertrophy (P < .01) compared with untreated controls. These data indicate that CVD is effective in delaying progression of renal damage and provides beneficial effects in the remnant kidney and cardiac hypertrophy, even at nonhypotensive doses.
Insights
Carvedilol (CVD) effectively slows nephrosclerosis progression and reduces cardiac hypertrophy in rats. These renoprotective effects occur even at non-hypotensive doses, demonstrating CVD
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Antihypertensive drugs exhibit varied effects on renal hemodynamics and morphology.
- Nephrosclerosis progression and cardiac hypertrophy are significant clinical concerns.
Purpose of the Study:
- To evaluate the renoprotective effects of carvedilol (CVD), a novel beta-blocker and vasodilator.
- To determine if CVD slows nephrosclerosis progression and reduces cardiac hypertrophy.
- To assess the dependency of these effects on blood pressure reduction levels.
Main Methods:
- A rat model of 5/6 nephrectomy (Nx) was used, with groups receiving varying doses of carvedilol (CVD) or placebo.
- Renal function was assessed via 24-hour urine protein and sodium excretion, and serum creatinine levels.
- Cardiac hypertrophy and renal morphology were evaluated histopathologically.
- Plasma renin activity and CVD levels were measured.
Main Results:
- Carvedilol significantly reduced 24-hour urine protein excretion in a dose-dependent manner.
- Significant decreases in blood pressure were observed at higher CVD doses (10 and 20 mg/kg/day).
- CVD treatment improved glomerular filtration rate, indicated by decreased serum creatinine and increased urinary sodium excretion.
- Both renal damage and cardiac hypertrophy were significantly reduced in CVD-treated rats compared to controls, irrespective of hypotensive effects.
Conclusions:
- Carvedilol demonstrates significant renoprotective properties, delaying nephrosclerosis progression in a rat model.
- CVD effectively reduces cardiac hypertrophy, a common comorbidity in renal disease.
- The beneficial effects of carvedilol on renal damage and cardiac hypertrophy are evident even at doses that do not significantly lower blood pressure.