phytoestrogens and Aortic-Diseases

Estrogen deficiency was produced in female Sprague-Dawley rats by surgical removal of both the ovaries and these animals were used 4 weeks later. Endothelium-dependent and endothelium-independent relaxations due to acetylcholine and sodium nitroprusside were observed respectively, in isolated rat thoracic aortic ring preparation. Extent of lipid peroxidation was measured by estimating serum TBARS. Integrity of vascular endothelium was assessed using hematoxylin and eosin staining. Generation of nitric oxide was measured indirectly, by estimating serum and urinary nitrite/nitrate concentration. Ovariectomy produced significant vascular endothelial dysfunction, measured in terms of reduced acetylcholine-induced endothelium-dependent vasorelaxation, serum and urinary nitrite/nitrate concentration and impairment of integrity of vascular endothelium. Administration of daidzein (0.2 mgkg(-1)day(-1), sc 0.4 mgkg(-1)day(-1), sc and 0.8 mgkg(-1)day(-1), sc) and Atorvastatin (30 mgkg(-1)day(-1), po Positive Control) for one week markedly improved vascular endothelial dysfunction due to increase in nitric oxide bioavailability perhaps by inhibiting caveolin-1 and activation of PI3K-AKT pathway.

Topics: Acetylcholine; Animals; Aorta, Thoracic; Aortic Diseases; Caveolin 1; Endothelium, Vascular; Female; Isoflavones; Nitrates; Nitrites; Nitroprusside; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Vasodilation; Vasodilator Agents

Previously, we demonstrated that intact female rats fed a standard rodent diet containing soybean products exhibit essentially no adverse left ventricular (LV) remodeling in response to aortocaval fistula-induced chronic volume overload. We hypothesized that phytoestrogenic compounds in the diet contributed to the female cardioprotection. To test this hypothesis, four groups of female rats were studied: sham-operated (Sham) and fistula (Fist) rats fed a diet with [P(+)] or without [P(-)] phytoestrogens. Eight weeks postfistula, systolic and diastolic cardiac function was assessed by using a blood-perfused, isolated heart preparation. High-phytoestrogen diet had no effect on body, heart, and lung weights, or cardiac function in Sham rats. Fistula groups developed LV hypertrophy, which was not reduced by dietary phytoestrogens [1,184 +/- 229 mg Fist-P(-) and 1,079 +/- 199 mg Fist-P(+) vs. 620 +/- 47 mg for combined Sham groups, P < 0.05]. Unstressed LV volume increased in Fist-P(-) rats (428 +/- 16 vs. 300 +/- 14 microl Sham, P < 0.0001), but it was not different from Sham for Fist-P(+) animals (286 +/- 17 microl). Fist-P(-) rats developed increased ventricular compliance (5.3 +/- 0.8 vs. 2.3 +/- 0.3 microl/mmHg Sham, P < 0.01), whereas Fist-P(+) rats had no change in compliance (2.8 +/- 0.4 mul/mmHg). Intrinsic ventricular contractility was maintained in the Fist-P(+) rats, but it was reduced (P < 0.001) in the Fist-P(-) rats [systolic pressure-volume slope: 1.04 +/- 0.03, 0.60 +/- 0.06, and 0.99 +/- 0.08 mmHg/microl, for Fist-P(+), Fist-P(-), and Sham, respectively]. These data indicate that dietary phytoestrogens contribute significantly to female cardioprotection against volume overload-induced adverse ventricular remodeling and that studies evaluating gender differences in cardiovascular remodeling must consider the influence of dietary phytoestrogens.

Topics: Animals; Aortic Diseases; Arteriovenous Fistula; Cardiac Output, Low; Cardiotonic Agents; Chronic Disease; Diet; Female; Hyperemia; Hypertrophy, Left Ventricular; Myocardial Contraction; Phytoestrogens; Rats; Rats, Sprague-Dawley; Sex Characteristics; Vena Cava, Inferior; Ventricular Remodeling