Relaxin ameliorates hypertension and increases nitric oxide metabolite excretion in angiotensin II but not N(ω)-nitro-L-arginine methyl ester hypertensive rats.
Relaxin ameliorates hypertension and increases nitric oxide metabolite excretion in angiotensin II but not N(ω)-nitro-L-arginine methyl ester hypertensive rats.
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DOI：
10.1161/hypertensionaha.110.164392
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发表时间：
2011-08
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影响因子：
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通讯作者：
Baylis C
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文献类型：
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作者：
Sasser JM;Molnar M;Baylis C
Previous findings suggest a potential therapeutic action of relaxin, the putative vasodilatory signal of normal pregnancy, in some forms of cardiovascular disease. However, the mechanisms underlying the beneficial effects of relaxin have not been fully elucidated. The purpose of this study was to determine if the vasodilatory effects of relaxin are dependent upon activation of nitric oxide synthase (NOS). We examined the effect of relaxin in male Sprague-Dawley rats given Angiotensin II (ANGII, 200ng/kg/min SC by minipump), the NOS inhibitor L-NAME (1.5 mg/100g iv followed by 150 mg/L in drinking water), or vehicle for 3 weeks. After 7 days of ANGII or L-NAME, mean arterial pressure (MAP) was elevated compared to baseline. Relaxin was administered (4 μg/h, SC by minipump) for the next 2 weeks of ANGII, L-NAME, or vehicle treatment. Two-week relaxin treatment alone slightly reduced MAP in normotensive rats. Three weeks of either ANGII or L-NAME treatment alone produced hypertension, albuminuria, mild glomerular sclerosis, reduced NOx excretion, and increased oxidative stress (excretion of hydrogen peroxide and TBARS and renal cortex nitrotyrosine abundance). Relaxin reduced MAP, albumin excretion, and oxidative stress markers and preserved glomerular structure and NOx excretion in ANGII treated rats; however, relaxin did not attenuate these changes in the rats treated with L-NAME. None of the treatments affected protein abundance of neuronal or endothelial NOS in the kidney cortex. These data suggest that the vasodilatory effects of relaxin are dependent upon a functional NOS system and increased NO bioavailability possibly due to a reduction in oxidative stress.
