Renal impairment in deoxycorticosterone acetate‐salt hypertensive rats

Dallemagne, Catherine; Yu, Jennifer; Brown, Lindsay; Gobé, Glenda C.; Endre, Zoltán H.

doi:10.1046/j.1440-1797.2000.00013.x

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…The left kidney was removed and weighed and the incision site sutured. Uninephrectomised rats (UNX rats) were given either no further treatment or 1% NaCl in the drinking water with subcutaneous injections of DOCA (25 mg in 0.4 ml dimethylformamide every fourth day) (DOCA‐salt rats) ( Dallemagne et al ., 2000 ). Experiments were performed 14 or 28 days after surgery.…”

Section: Methodsmentioning

confidence: 99%

Reversal of cardiac dysfunction by selective ET‐A receptor antagonism

Allan

Fenning

Levick

et al. 2005

British J Pharmacology

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1 The effectiveness of a selective endothelin receptor-A (ET-A) antagonist, A-127722 (approximately 10 mg kg À1 day À1 as 200 mg kg À1 powdered food), to reverse existing cardiac remodelling and prevent further remodelling was tested in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. 2 Uninephrectomised rats (UNX) administered DOCA (25 mg every fourth day s.c.) and 1% NaCl in drinking water for 28 days developed hypertension (systolic blood pressure (BP): UNX 12876 mmHg, DOCA-salt 18275* mmHg; *Po0.05 vs UNX), left ventricular hypertrophy (UNX 1.9970.06 mg kg À1 body wt, DOCA-salt 3.3070.08* mg kg À1 body wt), decreased left ventricular internal diameter (UNX 6.6970.18 mm, DOCA-salt 5.5170.37* mm), an increased left ventricular monocyte/macrophage infiltration together with an increased interstitial collagen from 2.770.3 to 11.771.3%, increased passive diastolic stiffness (UNX 21.170.5, DOCA-salt 30.171.3*), prolongation of the action potential duration at 20 and 90% of repolarisation (APD 20 -UNX 6.871.1, DOCAsalt 10.171.5* ms; APD 90 -UNX 34.473.5 ms, DOCA-salt 64.3710.4* ms) and vascular dysfunctions (2.6-fold decrease in maximal contractile response to noradrenaline, 3.5-fold decrease in maximal relaxation response to acetylcholine). 3 Administration of A-127722 for 14 days starting 14 days after surgery attenuated the increases in systolic BP (15076** mmHg, **Po0.05 vs DOCA-salt), left ventricular wet weight (2.6570.06** mg kg À1 body wt) and internal diameter (6.3970.31** mm), prevented left ventricular monocyte/macrophage accumulation, attenuated the increased left ventricular interstitial collagen (7.671.3%**), reversed the increased passive diastolic stiffness (22.171.2**), attenuated the action potential duration prolongation (APD 20 -7.671.4**, APD 90 -41.576.9** ms) and normalised changes in vascular function. 4 ET-A receptor antagonism both reverses and prevents the cardiac and vascular remodelling in DOCA-salt hypertension and improves cardiovascular function.

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Section: Methodsmentioning

confidence: 99%

Reversal of cardiac dysfunction by selective ET‐A receptor antagonism

Allan

Fenning

Levick

et al. 2005

British J Pharmacology

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“…The left kidney was removed and weighed and the skin wound sutured. Uninephrectomized rats were given either no further treatment (UNX rats) or 1% NaCl in the drinking water with subcutaneous injections of deoxycorticosterone acetate (DOCA; 25 mg in 0.4 ml dimethylformamide every fourth day) (DOCA‐salt rats) (Dallemagne et al ., 2000). Experiments were performed 2 or 4 weeks after surgery.…”

Section: Methodsmentioning

confidence: 99%

Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA‐salt hypertensive rats

Mirkovic

Seymour

Fenning

et al. 2002

British J Pharmacology

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117

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1 This study has administered pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) or amiloride to attenuate the remodelling and associated functional changes, especially an increased cardiac stiness, in DOCA-salt hypertensive rats. body wt) without lowering systolic blood pressure. 4 Collagen deposition was signi®cantly increased in the interstitium after 2 weeks and further increased with scarring of the left ventricle after 4 weeks; pirfenidone and amiloride reversed the increases and prevented further increases. This accumulation of collagen was accompanied by an increase in diastolic stiness constant; both amiloride and pirfenidone reversed this increase. 5 Noradrenaline potency (positive chronotropy) was decreased in right atria (neg log EC50: control 6.92+0.06; DOCA-salt 6.64+0.08); pirfenidone but not amiloride reversed this change. Noradrenaline was a more potent vasoconstrictor in thoracic aortic rings (neg log EC50: control 6.91+0.10; DOCA-salt 7.90+0.07); pirfenidone treatment did not change noradrenaline potency. 6 Thus, pirfenidone and amiloride reverse and prevent cardiac remodelling and the increased cardiac stiness without reversing the increased vascular responses to noradrenaline. British Journal of Pharmacology (2002) 135, 961 ± 968

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“…The left kidney was removed and weighed, and the incision site was sutured. Uninephrectomized rats were given no further treatment or were given 1% NaCl in the drinking water with subcutaneous injections of DOCA (25 mg in 0.4 ml of dimethylformamide every 4th day, DOCA-salt rats) (13). LArginine was administered as a 5% mixture in powdered rat food, which was available ad libitum for 28 days.…”

Section: Doca-salt Hypertensive Ratsmentioning

confidence: 99%

“…LArginine was administered as a 5% mixture in powdered rat food, which was available ad libitum for 28 days. Experiments were performed 28 days after surgery, as in previous studies (2,9,13,27,33).…”

Section: Doca-salt Hypertensive Ratsmentioning

confidence: 99%

l-Arginine attenuates cardiovascular impairment in DOCA-salt hypertensive rats

Fenning¹,

Harrison²,

Rose’Meyer³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Nitric oxide (NO) is essential for normal function of the cardiovascular system. This study has determined whether chronic administration of l-arginine, the biological precursor of NO, attenuates the development of structural and functional changes in hearts and blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Uninephrectomized rats treated with DOCA (25 mg every 4th day sc) and 1% NaCl in the drinking water for 4 wk were treated with l-arginine (5% in food, 3.4 ± 0.3 g·kg body wt−1·day−1). Changes in cardiovascular structure and function were determined by echocardiography, microelectrode studies, histology, and studies in isolated hearts and thoracic aortic rings. DOCA-salt hypertensive rats developed hypertension, left ventricular hypertrophy with increased left ventricular wall thickness and decreased ventricular internal diameter, increased inflammatory cell infiltration, increased ventricular interstitial and perivascular collagen deposition, increased passive diastolic stiffness, prolonged action potential duration, increased oxidative stress, and inability to increase purine efflux in response to an increased workload. l-Arginine markedly attenuated or prevented these changes and also normalized the reduced efficacy of norepinephrine and acetylcholine in isolated thoracic aortic rings of DOCA-salt hypertensive rats. This study suggests that a functional NO deficit in blood vessels and heart due to decreased NO synthase activity or increased release of reactive oxygen species such as superoxide may be a key change initiating many aspects of the cardiovascular impairment observed in DOCA-salt hypertensive rats. These changes can be prevented or attenuated by administration of l-arginine.

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Renal impairment in deoxycorticosterone acetate‐salt hypertensive rats

Cited by 5 publications

References 31 publications

Reversal of cardiac dysfunction by selective ET‐A receptor antagonism

Reversal of cardiac dysfunction by selective ET‐A receptor antagonism

Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA‐salt hypertensive rats

l-Arginine attenuates cardiovascular impairment in DOCA-salt hypertensive rats

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