کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2553365 1560755 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Atrial natriuretic peptide prevents diabetes-induced endothelial dysfunction
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Atrial natriuretic peptide prevents diabetes-induced endothelial dysfunction
چکیده انگلیسی

Atrial natriuretic peptide (ANP) exerts beneficial effects on the cardiovascular system in part by exerting antioxidant activity. Given that oxidant stress is a key cause of endothelial dysfunction in diabetes, we investigated whether ANP improves endothelial function in rats with diabetes. Rats were injected with streptozotocin (55 mg/kg iv) to induce type 1 diabetes or the citrate vehicle as controls (n = 12). After 4 weeks the diabetic rats were treated with ANP (10 pmol/kg/min sc, n = 12) or the antioxidant tempol (1.5 mmol/kg/day sc, n = 11), both by osmotic minipump, ramipril (1 mg/kg per day in the drinking water) or remained untreated (n = 11). After a further 4 weeks, anaesthetised rats were killed by exsanguination and the thoracic aortae collected for examination of vascular activity and measurement of superoxide generation. Diabetic rats showed elevated plasma glucose concentration (45 ± 3 mM) compared to controls (10 ± 1 mM) and this was not affected by ANP (43 ± 3 mM), ramipril (41 ± 2 mM) or tempol (43 ± 2 mM). Endothelium-dependent relaxation ex vivo in response to acetylcholine was impaired in diabetic rats (Rmax = 66 ± 4%) compared to control rats (Rmax = 94 ± 1%) but treatment with ANP (Rmax = 80 ± 4%), ramipril (Rmax = 88 ± 2%) or tempol (Rmax = 81 ± 5%) significantly improved those responses. Relaxant responses to the endothelium-independent vasodilator sodium nitroprusside were enhanced by treatment of diabetic rats with ANP or ramipril and their combination; but not by tempol. Superoxide generation was significantly elevated in aorta from untreated diabetic rats (649 ± 146% of control). In diabetic rats, superoxide generation was significantly attenuated by ANP (to 229 ± 78%) or tempol (to 186 ± 64%). This study demonstrates that ANP improves vascular oxidant stress in concert with endothelial function, independent of any effect on plasma glucose levels. These studies may lead to new therapies, based on natriuretic peptide and/or antioxidant approaches, for ameliorating the vascular complications of diabetes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 82, Issues 15–16, 9 April 2008, Pages 847–854
نویسندگان
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