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自发性高血压大鼠绝经后高血压动物模型的特征

Characterization of an animal model of postmenopausal hypertension in spontaneously hypertensive rats.

作者信息

Fortepiani Lourdes A, Zhang Huimin, Racusen Lorraine, Roberts L Jackson, Reckelhoff Jane F

机构信息

Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-4505, USA.

出版信息

Hypertension. 2003 Mar;41(3 Pt 2):640-5. doi: 10.1161/01.HYP.0000046924.94886.EF. Epub 2002 Dec 9.

Abstract

Blood pressure (BP) increases in postmenopausal women. The mechanisms responsible are unknown. The present study was performed to characterize a model of postmenopausal hypertension in the rat and to determine the role that oxidative stress may play in mediating the postmenopausal hypertension. Spontaneously hypertensive rats were ovariectomized (ovx) or left intact (PMR) at 8 months and were aged to 18 months. These animals were compared with young females (YF; 4 or 8 months of age) and old males (18 months) for some measurements. Estradiol levels were decreased in PMR rats to levels not different from YF rats in proestrous or from old males. BP increased progressively with age in PMR rats but not in ovx or male rats, such that the gender difference in hypertension disappeared by 18 months. Glomerular filtration rate was lower in ovx and PMR rats than in YF rats. Renal plasma flow and renal vascular resistance were similar between YF and ovx rats, but lower and higher, respectively, in PMR rats. Serum testosterone increased by 60% in ovx rats and 400% in PMR rats compared with YF rats. Plasma renin activity also increased in PMR rats but not in ovx rats. Chronic treatment (for 8 months beginning at 8 months of age) of PMR rats with vitamins E and C, but not tempol, resulted in a significant reduction in BP and excretion of F2-isoprostanes. In contrast, tempol, but not vitamins E and C, reduced BP in old males. These data suggest that the PMR rats, but not ovx rats, may be a suitable model for the study of postmenopausal hypertension, and that oxidative stress plays a role in the increased BP.

摘要

绝经后女性的血压会升高。其相关机制尚不清楚。本研究旨在建立大鼠绝经后高血压模型,并确定氧化应激在介导绝经后高血压中可能发挥的作用。自发性高血压大鼠在8个月时进行卵巢切除(ovx)或保持完整(PMR),并饲养至18个月。将这些动物与年轻雌性大鼠(YF;4或8个月龄)和老年雄性大鼠(18个月龄)进行一些测量比较。PMR大鼠的雌二醇水平降低至与发情前期的YF大鼠或老年雄性大鼠无差异的水平。PMR大鼠的血压随年龄逐渐升高,而ovx大鼠或雄性大鼠则不然,以至于到18个月时高血压的性别差异消失。ovx和PMR大鼠的肾小球滤过率低于YF大鼠。YF大鼠和ovx大鼠的肾血浆流量和肾血管阻力相似,但PMR大鼠的肾血浆流量较低,肾血管阻力较高。与YF大鼠相比,ovx大鼠的血清睾酮增加了60%,PMR大鼠增加了400%。PMR大鼠的血浆肾素活性也增加,而ovx大鼠则没有。用维生素E和C(而非tempol)对PMR大鼠进行长期治疗(从8个月龄开始,持续8个月)可显著降低血压和F2-异前列腺素的排泄。相反,tempol可降低老年雄性大鼠的血压,但维生素E和C则不能。这些数据表明,PMR大鼠而非ovx大鼠可能是研究绝经后高血压的合适模型,并且氧化应激在血压升高中起作用。

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