Beneficial Effects of the Combination of Nifedipine and Losartan in Hypertensive Dahl Salt-Sensitive Rats

Abstract

The antihypertensive and organ-protective effects of the combination of the angiotensin II type 1 receptor blocker losartan and the calcium channel blocker nifedipine were examined in Dahl salt-sensitive rats. The rats fed with a high-salt diet developed hypertension accompanied by aorta and heart hypertrophy, and impaired renal function. The animals were treated with losartan (30 mg/kg/day), nifedipine (7.8 mg/kg/day) or with a combination of both drugs for 8 weeks. At the end of the study systolic blood pressure, kidney function, organ weight, and mRNA expression were investigated. Losartan reduced significantly the systolic blood pressure as well as the aorta and left ventricular hypertrophy. Nifedipine and its combination with losartan had similar effects on the systolic blood pressure, aorta and left ventricular hypertrophy but only the combination treatment reduced the expression of transforming growth factor-beta1 in aorta and brain natriuretic peptide in left ventricle significantly. Nifedipine and the combination therapy reduced proteinuria and improved urine creatinine excretion. The expression of collagen III and IV in the kidney was significantly reduced by the combination therapy. These results indicate that although losartan and nifedipine were effective in lowering blood pressure and showed moderate organ protection, additional benefits can be expected by combination therapy with both compounds.