Abstract

Blood pressure (BP) is one of the major determinants of cerebrovascular morbidity and mortality in individuals. Cell culture and animal model studies suggest the involvement of the renin-angiotensin system (RAS) in cerebral damage in stroke. Further, recently, interruption of the RAS with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II (Ang II) type 1 receptor blockers (ARBs) has been shown to reduce the risk for de novo or recurrent strokes in hypertensive patients. However, whether BP lowering independent effects of this class of agents could partly contribute to cerebral protection in stroke remains to be elucidated. In this study, ARBs, telmisartan and losartan, were given concomitantly for 5 weeks in spontaneously hypertensive rats stroke-prone (SHR-SP) infused with Ang II, and the effects of these agents on neurological deficits and survival were evaluated up to 25 weeks. There was no significant difference of BP levels among four groups (not-treated, Ang II-treated, Ang II plus telmisartan-treated, and Ang II plus losartan-treated rats) during the Ang II infusion period. Although both ARBs protected against neurological deficits and prolonged survival in Ang II-infused SHR-SP, the protective effects of telmisartan were stronger than those of losartan. Cumulative neurological deficit and death rates were significantly less in telmisartan-treated than in non-treated SHR-SP. The present findings suggest that ARBs could partly exert cerebral protection in a BP lowering independent manner and that inhibition of the RAS by telmisartan may become a promising strategy for the treatment of high-risk stroke-prone hypertensive patients.

Keywords: Telmisartan, losartan, stroke, hypertension, angiotensin II