Aldosterone-binding globulin-induced hypertension in the rat. A new experimental model.

Nowaczynski, M; Nowaczynski, W.; Mavoungou, D.; Lioy, Franco; Wilkins, G. E.; Fung, Kathryn; Boyko, William J.

doi:10.1161/01.hyp.5.6_pt_3.v163

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…9 In animal models involving increased sodium intake or aldosterone, previous investigations have shown that cardiac output is either normal or even increased at an early phase. 13 Thus, it seems likely that an increased ventricular ejection volume contributes to the increase in PP. One major question was to determine whether arterial stiffness could also participate in the increase in PP in this model.…”

Section: Model Of Uninephrectomized Aldo-salt Ratsmentioning

confidence: 99%

Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated Rats

et al. 2002

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Background-Previous studies have demonstrated the development of cardiac fibrosis in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on in vivo mechanical properties of the carotid artery using echo-tracking system. Methods and Results-Aldo was administered (1 g/h) in uninephrectomized Sprague-Dawley rats (SD) receiving a high-salt diet from 8 to 12 weeks of age. Uninephrectomized control SD rats received a normal salt diet without Aldo. Three groups of Aldo-salt rats were treated with 1, 10, or 30 mg/kg Ϫ1 · d Ϫ1 of Epl by gavage. Elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The structure of the arterial wall was analyzed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo produced increased systolic arterial pressure, pulse pressure, Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities compared with controls without Aldo. No differences in collagen mRNA levels were detected between groups. Epl blunted the increase in pulse pressure in Aldo rats and normalized Einc-wall stress curves, MCSA, and EIIIA Fn. These effects were dose dependent and not accompanied by a reduction in wall stress. Conclusions-Aldo is able to increase arterial stiffness associated with Fn accumulation, independently of wall stress. The preventive effects of Epl suggest a direct role for mineralocorticoid receptors in mechanical and structural alterations of large vessels in rat hyperaldosteronism.

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Section: Model Of Uninephrectomized Aldo-salt Ratsmentioning

confidence: 99%

Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated Rats

et al. 2002

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“…Inhibitors of corticosteroidogenesis also have been shown to be efficacious in the treatment of some forms of human hypertension (11). Finally, administration of corticoids to intact or adrenalectomized rats has been shown to produce hypertension (12)(13)(14).…”

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Adrenocortical Function in Deoxycorticosterone Acetate (DOCA)-Hypertensive Yucatan Miniature Swine

Carsia

Weber

Haight

et al. 1985

Experimental Biology and Medicine

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Adrenocortical function was assessed in six normal and six chronic (> 12 weeks), DOCA-hypertensive Yucatan miniature swine; mean arterial pressures were ll5.3 ± 11.7 and 163.6 ± 27.2 mm Hg, respectively (mean ± SEM). Adrenocortical function was evaluated in vivo by measuring changes in plasma cortisol and aldosterone in response to exogenous ACTH (0.25 mg, iv), and in vitro by measuring the responses of collagenase-isolated adrenocortical cells to ACTH and angiotensin II. Corticoids were measured by specific radioimmunoassay. Basal plasma cortisol values of conscious DOCA-hypertensive swine were approximately 53% of the values of normotensive swine (P < 0.05). However, ACTH induced a 419% increase in plasma cortisol values in DOCA-hypertensive swine compared to a 261% increase in the normotensive swine (P < 0.05). These differences between the two groups were not altered by anesthesia. There were no significant differencesin ACTH-induced changes in plasma aldosterone between the normotensive and DOCA-hypertensive swine. Experiments in vitro showed that the corticoid secretory responses of adrenocortical cells from DOCA-hypertensive animals were . 6 times more sensitive to ACTH and 3.2 times more sensitive to angiotensin II than those of cells from normotensive swine. Thus, despite the possibility of adrenocortical insufficiency due to suppressed plasma renin activity and the negative feedback of DOCA on the hypothalamichypophyseal-adrenal axis, adrenocortical function of DOCA-hypertensive swine was hyperresponsive to trophic hormones. Results from this study suggest that the DOCA-hypertensive swine may be a valuable model in elucidating the relationship between hypertension and adrenocortical function and in investigating nonclassical control of the adrenal cortex, that is, control exerted during the hypertensive state that exists apart from or in addition to that exerted by ACTH and angiotensin II.

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Renin Angiotensin Aldosterone Axis, Including Aldosterone Binding Globulin and Blood Pressure in Three Species of Nonhuman Primates

Mavoungou

Nowaczynski

et al. 1987

J of Medical Primatology

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Variables of renin‐angiotensin‐aldosterone axis with inclusion of protein binding to specific plasma globulin (ABG), plasma cortisol, and the blood pressure (BP) were measured in 24 chimpanzees, 4 gorillas, and 16 cynomolgus monkeys. ABG activity was readily detected in plasma from the primates. In chimpanzees and gorillas, all the variables under baseline conditions were similar to those in humans. In cynomolgus (Macaca fascicularis), both the ABG binding capacity for aldosterone and the diastolic or systolic BP were significantly higher (p < 0.001 and p < 0.01 respectively) than in chimpanzees and gorillas.

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Aldosterone-binding globulin-induced hypertension in the rat. A new experimental model.

Cited by 3 publications

References 24 publications

Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated Rats

Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated Rats

Adrenocortical Function in Deoxycorticosterone Acetate (DOCA)-Hypertensive Yucatan Miniature Swine

Renin Angiotensin Aldosterone Axis, Including Aldosterone Binding Globulin and Blood Pressure in Three Species of Nonhuman Primates

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