CARDIOVASCULAR EFFECTS OF A LOW-DOSE COMBINATION OF RAMIPRIL AND FELODIPINE IN SPONTANEOUSLY HYPERTENSIVE RATS

1 Cardiovascular effects of submaximal antihypertensive doses of the a ngiotensin converting enzyme inhibitor, ramipril (0.25 mg kg(-1) day(- 1) in the food), and the calcium channel blocker, felodipine (0.4 mg k g(-1) day(-1) subcutaneously by osmotic minipump), both alone and in c ombination, were examined in spontaneously hypertensive rats (SHR) in a four-week study. 2 Both ramipril and felodipine as monotherapy decre ased systolic blood pressure. The antihypertensive effect of the drug combination was more than that of ramipril treatment alone, but not si gnificantly better than that of felodipine monotherapy. Ramipril or fe lodipine treatments did not significantly affect the heart rate, eithe r alone or in combination. 3 The beneficial effect of ramipril monothe rapy on left ventricular hypertrophy was more prominent than that of f elodipine. The cardioprotective effect of felodipine was improved when combined to ramipril. The systolic blood pressure at the end of the e xperimental period correlated only weakly with left ventricular hypert rophy. 4 Responses of mesenteric arterial rings in vitro were examined at the end of the four-week study. Ramipril and felodipine monotherap ies as well as their combination markedly improved the endothelium-dep endent vascular relaxation responses to acetylcholine. The combination of ramipril and felodipine slightly enhanced the endothelium-independ ent vascular relaxation responses to sodium nitroprusside. Ramipril tr eatment alone slightly diminished the vascular contractile responses t o noradrenaline. Neither ramipril nor felodipine alone or in combinati on affected the vascular contractile responses to potassium chloride. 5 Ramipril treatment, both alone and in combination with felodipine, c aused a three fold increase in plasma renin activity. Serum aldosteron e, fasting blood glucose level, serum insulin and the 24 hour urinary excretions of sodium, potassium, magnesium, calcium, phosphorus or pro tein were not significantly affected by the drug treatments. 6 Our fin dings suggest that a better overall control of hypertension and end-or gan damages, without an increase in adverse effects, can be achieved b y the combination of submaximal antihypertensive doses of felodipine a nd ramipril than by monotherapy with either drug alone.