effect of diazepam on the hypotensive action of captopril in anasthetized normotensive rats-the role of prostaglandins and angiotensin I converting enzyme

ABSTRACT

The effects of acute administration of captopril [1 mg/kg] and/or diazepam [5 mg/kg] on blood pressure and heart rate of normotensive and indomethacin pretreated rats as well as the dose-response curves of angiotensin I and II were investigated. The subacute administration of captopril and/or diazepam on blood pressure and heart rate were also studied. In the acute study diazepam prolonged the duration of the captopril-induced hypotension, while captopril abolished the diazepam-induced bradycardia. These actions have not been affected by pretreatment with indomethacin. The dose-response curve of angiotensin II was not affected by administration of captopril and/or diazepam, while that of angiotensin I was shifted to the right in response to captopril and/or diazepam in synergetic manner. Subacute administration of captopril significantly reduced blood pressure and heart rate. Similarly, subacute treatment with diazepam induced slight reduction in blood pressure and heart rate and reduced the hypertensive action of captopril. Captopril abolished the diazepam-induced bradycardia. The present study revealed that diazepam prolongs the hypotensive action of captopril, possibly by a synergetic inhibitory effect on angiotensin I converting enzyme with no saralasin-like or prostaglandin-synthesis modulating action