NEPHROPROTECTION BY LONG-TERM ACE-INHIBITION WITH RAMIPRIL IN SPONTANEOUSLY HYPERTENSIVE STROKE-PRONE RATS

Background. The effect of life-long treatment with the ACE inhibitor r amipril on hypertension-induced histological changes in the kidney was tested in stroke-prone spontaneously hypertensive rats (SHR-SP). Meth ods. One-month-old pre-hypertensive SHR-SP were randomized into three groups of 45 animals each, and exposed via drinking water for their li fetime to a dose of: 1 mg.kg(-1).d(-1) ramipril (antihypertensive dose , HRA); 10 mu g.kg(-1).d(-1) slight dose of ramipril (non-antihyperten sive dose, LRA); or placebo. Histological and biochemical assessments were conducted after 15 months in ten rats each, when about 80% of the placebo group had died. Results. Kidneys from placebo treated SHR-SP showed pronounced arterial wall hypertrophy and sclerosis, arterial fi brinoid necrosis, glomerulopathy and tubular interstitial injury that were, in concert with normalized blood pressure, completely prevented by HRA treatment. LRA treatment did not affect any blood pressure incr ease, and also attenuated the development of arterial wall hypertrophy , sclerosis and arterial fibrinoid necrosis, though to a minor extent only, but did not change glomerular and tubulointerstitial degeneratio n. These effects of ramipril were associated with a dose-dependent inh ibition of plasma and renal tissue ACE activities as well as lower ser um concentrations of creatinine, but there were no changes in serum po tassium. Conclusions. Life-long HRA-induced ACE inhibition protects ag ainst hypertension-induced renal damages in SHR-SP. This is associated with a doubeling of the lifespan in these animals [1].