Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes.

Gavras, Haralambos; Brunner, Hans R.; Laragh, John H.; Vaughan, E. Darracott; Koss, Michael N.; Côté, Lucien J.; Gavras, Irène

doi:10.1161/01.res.36.2.300

Cited by 189 publications

(97 citation statements)

References 31 publications

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“…10) In the present study, both the heart weight-to-body weight ratio and the left ventricular weight-to-body weight ratio were markedly increased by the treatment with DOCA and salt, but BEC feeding produced significant lowering effects on these alterations. The view stated above also may be applicable to the relationship between the changes in blood pressure and the cardiac hypertrophy.…”

Section: Discussionsupporting

confidence: 39%

Antihypertensive Effects of Chicken Extract against Deoxycorticosterone Acetate-Salt-Induced Hypertension in Rats.

Matsumura

Okui

Ono³

et al. 2001

Biological & Pharmaceutical Bulletin

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In some Asian regions, particularly in Chinese communities in Southeast Asia, Brand's Essence of Chicken (BEC) is used as a traditional health food for various purposes, including recovery from postpartum sickness, the physical development of athletes, recovery from mental stress and enhancement of the mental efficiency of students. 1) However, little is known as to whether the supplement of BEC has a beneficial effect against the development and progression of cardiovascular diseases such as hypertension. The present study was designed to evaluate whether a dietary supplement of BEC has a preventive effect in the development of experimental hypertension induced by deoxycorticosterone acetate (DOCA) and salt, which has been used extensively as a useful model of human hypertension. We report here that dietary BEC can markedly suppress the elevation of blood pressure, cardiovascular hypertrophy and renal damage in DOCA-salt hypertensive rats. MATERIALS AND METHODSMaterials BEC (70 ml/bottle, Cerebos Pacific, Ltd., Singapore) was freeze-dried, and the resultant powder (about 6 g from 1 bottle of BEC) was mixed with normal commercial diet (NMF, Oriental Yeast Co., Ltd.) at 0.1 w/w% (BEC-containing diet). A feeding of this diet (15-30 g/rat/d) is equal to a dosage of about 0.175-0.35 ml of BEC/rat/d, and corresponds to approximately half to one bottle of BEC/human/ day.Animal Experiments Male Sprague-Dawley rats (6 weeks old) were anesthetized with sodium pentobarbital (40 mg/kg, i.p.) and the right kidney was removed via a right flank incision. After a 1-week postsurgical recovery period, rats were separated into a sham-operated group and a DOCA-salt group. The latter was further separated into a normal diet group and a BEC-containing diet group. The sham group was fed a normal diet and tap water ad libitum. Rats of the DOCA-salt group were treated twice weekly with DOCA suspended in corn oil, which was administered subcutaneously (15 mg/kg), and 1% NaCl was added to their tap water for drinking. Systolic blood pressure (SBP) was monitored weekly by a tail cuff and a pneumatic pulse transducer (BP-98A, Softron, Tokyo, Japan). After 5 weeks, the animals were placed in metabolic cages, urine was collected overnight, and then all rats were bled from the abdominal aorta to obtain blood samples. The heart, left kidney and aorta were excised and weighed. The thoracic aorta and left kidney were used for morphometric analysis.Histological Studies The thoracic aorta and the left kidney of each rat was preserved in phosphate-buffered 10% formalin, after which the tissues were chopped into small pieces, embedded in paraffin, cut at 4 mm and stained with hematoxylin and eosin. Three different cross sections of each vessel placed under a microscope were photographed, and the vessel wall area and thickness were determined using an image analyzer (AE-6905C, ATTO, Tokyo).Statistical Analysis All values were expressed as meanϮS.E.M. For statistical analysis, we used one-way ANOVA followed by Tukey-Kramer multiple comparison tests. F...

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Section: Discussionsupporting

confidence: 39%

Antihypertensive Effects of Chicken Extract against Deoxycorticosterone Acetate-Salt-Induced Hypertension in Rats.

Matsumura

Okui

Ono³

et al. 2001

Biological & Pharmaceutical Bulletin

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“…Recently, it has been reported that there is a remarkably high level of superoxide in the aortas of DOCA-salt hypertensive rats, 14,15 a model characterized by its depressed plasma renin activity. 16 These latter studies suggest that Ang II is not a sole stimulus of superoxide and raise the possibility that the increased superoxide in DOCA-salt hypertension may contribute to vascular adhesion molecule expression, such as VCAM-1. The present study addressed such a possibility and demonstrated a significant increase of arterial VCAM-1 expression and superoxide level in DOCA-salt hypertensive rats.…”

Section: Discussionmentioning

confidence: 99%

“…16 NO possesses important antihypertensive and antiatherogenic effects, including vasodilatation, 22 inhibition of VCAM-1 expression, 7 NF-B activation, 23 platelet adhesion, and smooth muscle proliferation. 22 NO-dependent vasodilatation is markedly impaired in atherosclerosis and hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…13 Two recent studies have indicated that there is also a substantial increase of vascular superoxide with reduced NO release in deoxycorticosterone acetate (DOCA)-salt hypertension, 14,15 a model well known for its suppressed plasma renin and angiotensin levels. 16 However, the level of vascular VCAM-1 expression has never been investigated in this model of hypertension.…”

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confidence: 99%

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Gene Transfer of Endothelial NO Synthase and Manganese Superoxide Dismutase on Arterial Vascular Cell Adhesion Molecule-1 Expression and Superoxide Production in Deoxycorticosterone Acetate-Salt Hypertension

Crockett

Wang

et al. 2002

ATVB

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Abstract-Enhanced vascular cell adhesion molecule-1 (VCAM-1) expression directly contributes to vascular dysfunction in hypertension. Decreased NO and/or increased superoxide are causative factors for such an event in the vessel wall. The present study was undertaken to determine whether gene transfer of endothelial NO synthase (eNOS) or manganese superoxide dismutase (MnSOD) affects VCAM-1 levels in arteries from hypertensive rats. Isolated carotid and femoral arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats were transduced for 4 hours with adenoviral vectors encoding eNOS, MnSOD, or ␤-galactosidase reporter genes. Recombinant eNOS or MnSOD expression was evident morphologically and quantitatively 24 hours after gene transfer. Immunohistochemistry, ELISA, and Western blot techniques were used to determine VCAM-1 expression and levels. In addition, endogenous eNOS and MnSOD and in situ superoxide levels were analyzed by immunoblotting and fluorescence confocal microscopy, respectively. Arterial VCAM-1 expression was significantly higher in DOCA-salt hypertensive rats than in sham-operated rats; this expression was accompanied by decreased MnSOD but unaltered endogenous eNOS levels. VCAM-1 expression was significantly lower in MnSOD-and eNOS-transduced hypertensive arteries, with a concomitant reduction of superoxide level. These results suggest that gene transfer of MnSOD or eNOS suppresses arterial VCAM-1 expression in DOCA-salt hypertension by reducing the superoxide level. A lthough hypertension is one of the key risk factors for atherosclerosis, the underlying molecular and cellular mechanisms remain to be delineated. 1 Enhanced adhesion molecule expression is known to contribute directly to vascular dysfunction in hypertension. 2 Vascular cell adhesion molecule-1 (VCAM-1) is an early marker of endothelial activation and dysfunction, leukocyte infiltration, and vascular remodeling in the development of early atherosclerotic lesions (fatty streaks and fibrous plaques). 2-5 Although VCAM-1 is structurally similar to intercellular adhesion molecule-1 and other adhesion molecules, its pattern of expression is unique. It exhibits low to negligible expression under baseline conditions but is profoundly upregulated by proatherosclerotic conditions in animal models and in humans. [2][3][4][5] In addition, compared with other adhesion molecules whose expression often extends into uninvolved and/or lesion-protected regions of the vessel wall, VCAM-1 expression is largely restricted to atherosclerotic lesions and lesionpredisposed regions. 2-5 Consistent with these phenomena, a recent study has demonstrated that VCAM-1, but not intercellular adhesion molecule-1 (ICAM-1), plays a critical role in early atherogenesis. 6 Enhanced adhesion molecule expression has been ascribed to an imbalance between oxidative stress and antioxidant activity. Experimental evidence suggests that NO and superoxide are 2 key regulating factors for the expression of adhesion molecules, including VCAM-1. 7,8 In angiotensi...

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“…Several animal models have been generated to investigate the pathophysiology of hypertensive vascular injury. Most animal models of MH to date require surgical or pharmacological intervention to precipitate onset or depend on the constitutive expression of endogenous genes or heterologous transgenes (2)(3)(4)(5). In rats doubly transgenic for human renin and angiotensinogen genes, hypertension and fibrinoid vasculitis (5) accompanied by alteration in surface adhesion molecules, proinflammatory cytokines, fibrogenic mediators and leukocyte infiltration (6) have been reported.…”

mentioning

confidence: 99%

Controlled Hypertension, a Transgenic Toggle Switch Reveals Differential Mechanisms Underlying Vascular Disease

Kantachuvesiri¹,

Fleming²,

Peters³

et al. 2001

Journal of Biological Chemistry

142

297

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A novel inbred rat model with inducible hypertension has been generated using a renin transgene under the transcriptional control of the cytochrome P450, Cyp1a1 promoter. The degree and duration of hypertension are regulated tightly by administration of the natural xenobiotic indole-3 carbinol and can be readily reversed. Induction experiments reveal distinct temporal and mechanistic responses to hypertensive injury in different vascular beds, which is indicative of differential susceptibility of organs to a hypertensive stimulus. The mesentery and heart exhibited the greatest sensitivity to damage, and the kidney showed an adaptive response prior to the development of malignant hypertensive injury. Quantitative analysis of morphological changes induced in mesenteric resistance arteries suggest eutrophic remodeling of the vessels. Kinetic evidence suggests that locally activated plasma prorenin may play a critical role in mediating vascular injury. This model will facilitate studies of the cellular and genetic mechanisms underlying vascular injury and repair and provide a basis for the identification of novel therapeutic targets for vascular disease.Essential hypertension has a complex multifactorial phenotype. Both genetic and environmental factors influence its development, and understanding the pathogenesis of complications such as vascular lesions and end-organ damage may lead to more specific treatment and targeted intervention.We have identified candidate loci in rats that may contribute to target organ damage and mortality in malignant hypertension (MH), 1 a condition characterized by an accelerated rise in blood pressure, endothelial injury, activation of the reninangiotensin system, and microangiopathy (1). Several animal models have been generated to investigate the pathophysiology of hypertensive vascular injury. Most animal models of MH to date require surgical or pharmacological intervention to precipitate onset or depend on the constitutive expression of endogenous genes or heterologous transgenes (2-5). In rats doubly transgenic for human renin and angiotensinogen genes, hypertension and fibrinoid vasculitis (5) accompanied by alteration in surface adhesion molecules, proinflammatory cytokines, fibrogenic mediators and leukocyte infiltration (6) have been reported. In most of these models, the onset of disease cannot be determined precisely.The initiation events of pathological processes can only be studied in an animal model in which hypertension is induced by tightly temporally regulated gene expression. If the onset and level of hypertension can be controlled, then the cellular and molecular events during initiation of the vascular and organ injury can be identified unequivocally. Reversibility of the gene expression provides an opportunity to study the molecular and cellular basis of repair. We therefore have generated inbred transgenic rats with inducible hypertension using the cytochrome P450 promoter, Cyp1a1, to drive expression of the mouse Ren-2 gene. The transgene is expressed primarily ...

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Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes.

Cited by 189 publications

References 31 publications

Antihypertensive Effects of Chicken Extract against Deoxycorticosterone Acetate-Salt-Induced Hypertension in Rats.

Antihypertensive Effects of Chicken Extract against Deoxycorticosterone Acetate-Salt-Induced Hypertension in Rats.

Gene Transfer of Endothelial NO Synthase and Manganese Superoxide Dismutase on Arterial Vascular Cell Adhesion Molecule-1 Expression and Superoxide Production in Deoxycorticosterone Acetate-Salt Hypertension

Controlled Hypertension, a Transgenic Toggle Switch Reveals Differential Mechanisms Underlying Vascular Disease

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