POTENTIATION OF THE HYPOTENSIVE EFFECT OF CAPTOPRIL BY THE H2 BLOCKER CIMETIDINE IN THE NORMOTENSIVE ANAESTHETIZED RATS

Document Type : Original Article

Authors

1 Department of Pharmacology, Faculty of Pharmacy, Zagazig University,Zagazig, Egypt

2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.

3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig and Cairo Universities - Egypt

Abstract

The effects of captopril (1 mg/kg), cimetidine (25 mg/kg), and their combination on the arterial blood pressure, heart rate, ECG and the calculated double product of anaesthetized normotensive rats were investigated. Results showed that captopril alone but not cimetidine significantly reduced the arterial blood pressure of rats. This effect lasted for 150 min. of administration. Captopril, cimetidine or their combination did not change the heart rate of rats. Administration of captopril in cimetidine-pretreated rats significantly reduced the arterial blood pressure and the calculated double product. Both the intensity and duration of the reduction in blood pressure were significantly greater than that induced by captopril alone, since the duration of this effect was extended for more than 180 min. after administration. This effect had two peaks, the first one came after 30 min. and the second one after 150 min. and the values of these reductions were 24% and 37%, respectively. Conclusively, cimetidine potentiates the hypotensive effect of captopril in anaesthetized rats. The mechanism of this positive interaction may be in part due to that cimetidine may increase the plasma levels of captopril through reduction of its rate of metabolism. This effect may result from the capability of cimetidine to inhibit cytochrome P450 enzymes which may be involved in type I biotransformation of captopril and consequently reduces its rate of degradation.

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