Can Sitaglipten Attenuate Hypertension, Myocardial Changes and Vascular Reactivity Induced by Long Term Blockade of Nitric Oxide Synthesis in the Rat?  

作　　者：Mervat E. Mohamed 

机构地区：[1]Umelqura University, Makkah Elmokaramah, Saudi Arabia

出　　处：《Open Journal of Endocrine and Metabolic Diseases》2014年第7期197-210,共14页内分泌与新陈代谢疾病期刊（英文）

摘　　要：Background: Glucagon-like peptide-1 (GLP-1) is an incretin hormone with insulinotropic properties that regulates glucose metabolism. GLP-1 receptors are the most extensively key modulators of lipid and glucose homeostasis. They are predominantly expressed in adipose tissues, some non adipose tissues including heart, kidney, spleen, and all relevant cells of the vasculature: endothelial cells, smooth muscle cells, and macrophages. The vascular distribution suggests their involvement in the control of cardiovascular function. Objective: The present experiment was designed to study the effect of sitaglipten alone or in combination with captopril on blood pressure, antioxidant enzymes, vascular reactivity and cardiac hypertrophy in NG-nitro-L-arginine methylester (L-NAME) induced hypertension in rats. Methods: One hundred male albino rats weighing from 150 - 200 g were included in this study. Rats were divided into two main groups. Group I, (20 rats) served as a control group for group II, and received 1 ml of physiological saline (0.9%), orally for seven weeks. Group II: hypertensive group, (80 rats) was given daily L-NAME in a dose of 40 mg/kg orally for seven weeks. Rats were further subdivided into A, B, C, and D, each of 20 rats. Group-A, received 1 ml of distilled water daily orally for six weeks, starting one week after L-NAME administration. Groups B, C and D were treated with daily sitaglipten (10 mg/kg b.wt. orally) and captopril (100 mg/kg b.wt. orally), alone or together for six weeks. Blood pressure, serum tumor necrosis factor-α (TNF-α), body weight (BW) and heart weight (HW) were measured. Malondialdehyde (MDA) and reduced glutathione (GSH) were estimated in cardiac tissues. Thoracic aorta was isolated and the aortic rings were allowed to achieve maximal tension by cumulative addition of phenylephrine (PE) (10-9-10-5 M) to the bath solution. Results: Sitaglipten and captopril, alone or together produced significant decreases in blood pressure and TNF-α. Higher oxidative stress accompanying hypertensBackground: Glucagon-like peptide-1 (GLP-1) is an incretin hormone with insulinotropic properties that regulates glucose metabolism. GLP-1 receptors are the most extensively key modulators of lipid and glucose homeostasis. They are predominantly expressed in adipose tissues, some non adipose tissues including heart, kidney, spleen, and all relevant cells of the vasculature: endothelial cells, smooth muscle cells, and macrophages. The vascular distribution suggests their involvement in the control of cardiovascular function. Objective: The present experiment was designed to study the effect of sitaglipten alone or in combination with captopril on blood pressure, antioxidant enzymes, vascular reactivity and cardiac hypertrophy in NG-nitro-L-arginine methylester (L-NAME) induced hypertension in rats. Methods: One hundred male albino rats weighing from 150 - 200 g were included in this study. Rats were divided into two main groups. Group I, (20 rats) served as a control group for group II, and received 1 ml of physiological saline (0.9%), orally for seven weeks. Group II: hypertensive group, (80 rats) was given daily L-NAME in a dose of 40 mg/kg orally for seven weeks. Rats were further subdivided into A, B, C, and D, each of 20 rats. Group-A, received 1 ml of distilled water daily orally for six weeks, starting one week after L-NAME administration. Groups B, C and D were treated with daily sitaglipten (10 mg/kg b.wt. orally) and captopril (100 mg/kg b.wt. orally), alone or together for six weeks. Blood pressure, serum tumor necrosis factor-α (TNF-α), body weight (BW) and heart weight (HW) were measured. Malondialdehyde (MDA) and reduced glutathione (GSH) were estimated in cardiac tissues. Thoracic aorta was isolated and the aortic rings were allowed to achieve maximal tension by cumulative addition of phenylephrine (PE) (10-9-10-5 M) to the bath solution. Results: Sitaglipten and captopril, alone or together produced significant decreases in blood pressure and TNF-α. Higher oxidative stress accompanying hypertens

关 键 词：Glucagon-Like Peptide-1 Glucagon-Like Peptide-1 Receptor INCRETIN Diabetes Blood Pressure Heart Failure VASODILATATION Sympathetic Activation L-Name Sitaglipten Renin Angiotensin System Captopril 

分 类 号：R5[医药卫生—内科学]