LOSARTAN IMPROVES ENDOTHELIAL FUNCTION OF CEREBRAL ARTERIOLES IN TYPE 1 DIABETES

Abstract

The goal of this study was to determine the role of angiotensin-1 (AT-1) receptors in impaired responses of cerebral arterioles during Type 1 diabetes mellitus (T1D). Using a cranial window technique, we measured the effects of topical application of losartan (0.1mM) on responses of pial arterioles to eNOS-dependent (acetylcholine and ADP) and –independent (nitroglycerin) agonists in nondiabetic and streptozotocin-induced diabetic rats. Protein expression of AT-1 receptors in cerebral arterioles and superoxide production (lucigenin) in brain tissue from nondiabetic and diabetic rats was also measured. We found that responses of pial arterioles to acetylcholine and ADP, but not to nitroglycerin, were impaired during T1D. Further, although losartan did not affect responses in nondiabetic rats, we found that losartan could reverse impaired responses of cerebral arterioles in diabetic rats. Losartan did not influence responses of arterioles to nitroglycerin in nondiabetic or diabetic rats. In addition, we found that the protein expression of AT-1 receptors was increased by T1D. Finally, we found that superoxide production was increased in diabetic compared to nondiabetic rats under basal conditions and that losartan inhibited this basal production of superoxide. We suggest that activation of AT-1 receptors during T1D can contribute to impaired eNOS-dependent responses of cerebral arterioles.