CHRONIC TREATMENT WITH LOSARTAN AMELIORATES VASCULAR DYSFUNCTION INDUCED BY AGING IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective To evaluate the effects of prolonged treatment with losartan on endothelium-dependent and endothelium-independent relaxations of a ortic rings from adult and senescent spontaneously hypertensive rats, and to clarify whether these effects were due to specific mechanisms o f the drug or a consequence of its blood-pressure-lowering action. Mat erials and methods Adult (aged 5 months) and senescent (aged 20 months ) male spontaneously hypertensive rats were treated for 12 consecutive weeks with 10 mg/kg per day losartan, Systolic blood pressure and pla sma concentration of nitrates were evaluated. We studied endothelium-d ependent and endothelium-independent relaxations and response to angio tensin II of aortic rings from rats of each group. The direct effects of angiotensin II type 1 receptor antagonism on vascular reactivity of aortic rings from untreated adult and senescent rats that had been in cubated beforehand with losartan were also studied. Results Losartan t reatment comparably reduced blood pressure and increased plasma concen tration of nitrates in rats of both age groups. Responses to acetylcho line and sodium nitroprusside were lower for rings from senescent than they were for rings from adult rats. Constrictor responses to angiote nsin II were higher for rings from senescent than they were for rings from adult rats. Treatment with losartan increased the magnitude of re laxations in response to acetylcholine for rings from rats in both gro ups, but increased the magnitude of relaxations in response to nitropr usside only for rings from senescent spontaneously hypertensive rats. incubation beforehand of aortic rings from untreated rats with losarta n enhanced magnitude of relaxations in response both to acetylcholine and to nitroprusside only for rings from senescent spontaneously hyper tensive rats. Conclusions The consequences of aging for endothelium-de pendent and endothelium-independent relaxations of rings from spontane ously hypertensive rats are ameliorated by losartan treatment, suggest ing that angiotensin II plays a role via type 1 receptors, The effects of losartan on senescent spontaneously hypertensive rats were due not only to its blood-pressure-lowering action but also to the blockade o f specific mechanisms derived from angiotensin II type 1 receptor anta gonism, which might involve an increase in availability of NO. (C) 199 8 Lippincott-Raven Publishers.