INFLUENCE OF AGE AND DIETARY-SODIUM ON THE CARDIOVASCULAR AND RENAL EFFECTS OF RAMIPRIL IN SPONTANEOUSLY HYPERTENSIVE RATS

The aim of the present study was to investigate the influence of age a nd an increased intake of dietary sodium on the cardiovascular and ren al effects of the angiotensin converting enzyme inhibitor, ramipril. M ale spontaneously hypertensive rats (SHR) aged 10 and 60 weeks receive d either control or a high level of sodium (0.3% vs 2.6% Na) and ramip ril (2 mg/kg/day) mixed in the chow for 6 weeks. Blood pressure was me asured weekly by tail-cuff method. Arterial functions were determined by measuring vascular contractile and relaxation responses of mesenter ic arterial rings in vitro at the end of the study. An age-related inc rease in systolic blood pressure, left ventricular (LVH) and renal hyp ertrophy (RH) as well as proteinuria were found in SHR. The vascular r elaxation to nitroprusside was impaired in aged SHR. The high sodium i ntake accelerated the development of hypertension only in young SHR bu t increased LVH and RH in both age groups. Ramipril effectively lowere d blood pressure in both age groups, but decreased the LVH significant ly only in young rats. Ramipril markedly improved the vascular relaxat ion to acetylcholine and nitroprusside only in young rats. The vascula r contractile responses to noradrenaline and potassium chloride were n ot affected by age, sodium intake or ramipril treatment. The high sodi um intake markedly attenuated the cardiovascular effects of ramipril. The high-sodium diet enhanced the urinary excretion of cyclic GMP in b oth age groups, while it increased urinary excretion of protein in you ng SHR only. In conclusion, the cardiovascular effects of ramipril wer e impaired with advanced age even in the present of a control intake o f sodium. A high sodium intake attenuated or even abolished the cardio vascular effects of ramipril in both young and aged SHR.