INFLUENCE OF DIETARY SALTS ON THE CARDIOVASCULAR EFFECTS OF LOW-DOSE COMBINATION OF RAMIPRIL AND FELODIPINE IN SPONTANEOUSLY HYPERTENSIVE RATS

1 In spontaneously hypertensive rat (SHR) we examined over a 4-week pe riod the influence of control low sodium diet, common salt-enriched di et (sodium chloride 6% of the dry weight of the chow) and a novel mine ral salt-enriched diet (potassium-, magnesium-, and 1-lysine-enriched mineral salt added at a 75% higher level of 10.5% to produce the same sodium chloride concentration of 6%) on the cardiovascular effects pro duced by a low-dose combination of an angiotensin converting enzyme in hibitor ramipril (0.25 mg kg(-1) day(-1) in the food) and a calcium ch annel blocker felodipine (0.4 mg kg(-1) day(-1) subcutaneously via an osmotic minipump). 2 Common salt, but not the mineral salt, accelerate d the development of hypertension and induced left ventricular and ren al hypertrophy in SHR. Neither common salt nor mineral salt significan tly affected heart rate. 3 The combination of ramipril and felodipine decreased systolic blood pressure and prevented the development of lef t ventricular hypertrophy effectively during the common salt diet with out any significant effect on the heart rate. The cardiovascular effec ts of the drug combination were improved by the low sodium diet or by replacement of high common salt in the diet by mineral salt. 4 Respons es of endothelium-intact mesenteric arterial rings in vitro were exami ned at the end of the four-week study. The combination of ramipril and felodipine markedly improved the endothelium-dependent vascular relax ation responses to acetylcholine and enhanced the endothelium-independ ent vascular relaxation responses to sodium nitroprusside in SHR on co ntrol and common salt diets. Replacement of common salt in the diet by mineral salt improved the endothelium-dependent vascular relaxation r esponses to acetylcholine. The drug combination attenuated the alpha-a drenoceptor-mediated vascular contractile responses to noradrenaline d uring the common salt diet. 5 Ramipril and felodipine in combination i ncreased plasma renin activity by 1.9-3.2 fold without affecting serum aldosterone levels. 6 Our findings suggest that the cardiovascular ef fect of the low-dose combination of ramipril and felodipine was mainta ined during high salt intake. However, salt restriction or replacement of common salt in the diet by the potassium- and magnesium-enriched m ineral salt improved the cardiovascular effects of the drug combinatio n. In the face of a high intake of sodium, a part of the beneficial ca rdiovascular effects of the drug combination is apparently mediated by improved endothelium-dependent and endothelium-independent vascular r elaxation responses and attenuated alpha-adrenoceptor-mediated vascula r contractile responses.