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Rosiglitazone, a peroxisome proliferator‐activated receptor γ stimulant, abrogates diabetes‐evoked hypertension by rectifying abnormalities in vascular reactivity
Author(s) -
ElBassossy Hany M,
AboWarda Shaymaa M,
Fahmy Ahmed
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2012.05724.x
Subject(s) - rosiglitazone , medicine , endocrinology , diabetes mellitus , streptozotocin , phenylephrine , nitric oxide , blood pressure
Summary In addition to insulin sensitization, rosiglitazone exhibits favourable circulatory effects. In the present study, we tested the hypothesis that rosiglitazone protects against hypertension and vascular derangements caused by diabetes. Diabetes was induced by a single bolus injection of streptozotocin (50 mg/kg, i.p.). After 2 weeks, rats were started on a treatment regimen of 5 mg/kg rosiglitazone daily for a period of 6 weeks. The control group consisted of rats treated with vehicle (distilled water) for the same period of time. After 6 weeks treatment, blood pressure ( BP ) was recorded and serum levels of glucose, advanced glycation end‐products ( AGE ), triglycerides, total cholesterol and low‐density lipoprotein–cholesterol ( LDL ‐C) were determined. In in vitro experiments, concentration–response curves were constructed to phenylephrine ( PE ), KC l and acetylcholine ( AC h) in thoracic aorta rings. In addition, AC h‐induced nitric oxide ( NO ) generation and KC l‐induced intracellular Ca accumulation were determined in the aorta. Compared with values in control rats, both diastolic and systolic BP were increased in diabetic rats. Rosiglitazone treatment of diabetic rats abolished the increase in diastolic BP and significantly reduced the increased systolic BP without affecting the development of hyperglycaemia. The possibility that changes in vascular reactivity and/or lipid profile contributed to the effects of rosiglitazone on BP in diabetic rats was investigated. In aortic rings from diabetic rats, contractile responses to KC l were increased, whereas the relaxant responses to AC h were decreased. In rings from diabetic rosiglitazone‐treated rats, the exaggerated response to KC l and the impaired response to AC h were abolished. Furthermore, rosiglitazone abrogated impaired AC h‐stimulated NO generation in aortas isolated from diabetic rats. Diabetes in rats was accompanied by elevated levels of triglycerides, total cholesterol, LDL ‐C and AGE . Rosiglitazone treatment abrogated the increased levels of triglycerides, total cholesterol and LDL ‐C, but only partially reduced AGE levels. Collectively, these observations indicate that rosiglitazone abrogates diabetes‐evoked hypertension by ameliorating detrimental changes in vascular reactivity and lipid profiles.