Characterization of an Animal Model of Postmenopausal Hypertension in Spontaneously Hypertensive Rats

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2003-03, Vol.41 (3, Part 2 Suppl), p.640-645
• Main Authors: Fortepiani, Lourdes A, Zhang, Huimin, Racusen, Lorraine, Roberts, L Jackson, Reckelhoff, Jane F
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Antioxidants - pharmacology; Arterial hypertension. Arterial hypotension; Ascorbic Acid - pharmacology; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Cyclic N-Oxides - pharmacology; Disease Models, Animal; Estradiol - blood; Experimental diseases; Female; Hemodynamics; Hypertension - blood; Hypertension - etiology; Hypertension - physiopathology; Kidney - drug effects; Kidney - physiopathology; Male; Medical sciences; Ovariectomy; Oxidative Stress; Postmenopause; Rats; Rats, Inbred SHR; Spin Labels; Vaginal Smears; Vitamin E - pharmacology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000046924.94886.EF

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.