Losartan improves impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in type 1 diabetic rats.

Brain Research
Denise M ArrickWilliam G Mayhan

Abstract

We examined whether activation of angiotensin-1 receptors (AT1R) could account for impaired responses of cerebral arterioles during type 1 diabetes (T1D). First, we measured responses of cerebral arterioles in nondiabetic rats to eNOS-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists before and during application of angiotensin II. Next, we examined whether losartan could improve impaired responses of cerebral arterioles during T1D. In addition, we harvested cerebral microvessels for Western blot analysis of AT1R protein and measured production of superoxide anion by brain tissue under basal conditions and in response to angiotensin II in the absence or presence of losartan. We found that angiotensin II specifically impaired eNOS-dependent reactivity of cerebral arterioles. In addition, while losartan did not alter responses in nondiabetics, losartan restored impaired eNOS-dependent vasodilatation in diabetics. Further, AT1R protein was higher in diabetics compared to nondiabetics. Finally, superoxide production was higher in brain tissue from diabetics compared to nondiabetics under basal conditions, angiotensin II increased superoxide production in nondiabetics and diabetics, ...Continue Reading

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Citations

Feb 22, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Frank M Faraci
May 26, 2012·Journal of Applied Physiology·Sophocles ChrissobolisFrank M Faraci
Oct 22, 2008·Trends in Molecular Medicine·Sophocles Chrissobolis, Frank M Faraci
Feb 9, 2012·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Negara Tajbakhsh, Elke M Sokoya
Mar 26, 2016·Frontiers in Pharmacology·T Michael De Silva, Alyson A Miller
Mar 19, 2016·Cellular and Molecular Neurobiology·T Michael De Silva, Frank M Faraci
Jul 16, 2013·Free Radical Biology & Medicine·Mariam El AssarLeocadio Rodríguez-Mañas
Feb 6, 2017·Circulation Research·Xiaoming HuFrank M Faraci
Nov 24, 2017·Free Radical Research·Cezary GrochowskiRyszard Maciejewski
Mar 1, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Abdelrahman Y FoudaAdviye Ergul
Jun 11, 2021·Stroke; a Journal of Cerebral Circulation·T Michael De SilvaFrank M Faraci
Mar 27, 2021·Physiological Reviews·Jurgen A H R ClaassenFrank M Faraci

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