Beneficial effects of the combination of nifedipine and losartan in hypertensive Dahl salt-sensitive rats.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Product Related Research, Pharmacology, Pharma R&D Discovery Research, Bayer HealthCare AG, Wuppertal, Germany. hanna.tinel@bayerhealthcare.com
Hanna
H
Tinel
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy; D007668:Kidney / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D002121:Calcium Channel Blockers; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D053773:Transforming Growth Factor beta1; D020097:Natriuretic Peptide, Brain; D009543:Nifedipine; D019808:Losartan