Impaired Endothelium-Dependent Regulation of Ventricular Relaxation in Pressure-Overload Cardiac Hypertrophy

MacCarthy, Philip; Shah, Ajay

doi:10.1161/01.cir.101.15.1854

Cited by 56 publications

(47 citation statements)

References 51 publications

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“…Previous reports have suggested that the relaxant effect of NO is impaired in hypertrophied myocardium. 26) Our model of cardiac hypertrophy by volume-overload was accompanied by diastolic dysfunction even in the chronic inhibition of NO synthesis. In this volume-overload model, we reported that diastolic dysfunction was associated with the reduced gene expression of Ca 2+ cycling proteins.…”

Section: Discussionmentioning

confidence: 91%

Role of Nitric Oxide in the Progression of Cardiovascular Remodeling Induced by Carotid Arterio-Venous Shunt in Rabbits.

et al. 2003

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SUMMARYDespite a variety of biological roles for nitric oxide (NO) in the cardiovascular system, little is known about whether NO is involved in cardiac hypertrophy. We hypothesized that NO production following a sustained increase in shear stress by volumeoverload modifies the level of cardiac hypertrophy independent of hemodynamic changes. Volume-overload was induced by shunt formation between the left common carotid artery and the external jugular vein in 21 rabbits. These shunt rabbits were randomly assigned to 3 groups: shunt with no treatment (n=8), shunt treated with a low dose of N G -nitro-Larginine methyl ester (L-NAME, 0.5 g/L in drinking water, n=8), and shunt with a high dose of L-NAME (1.5 g/L, n=5). Eight sham operated rabbits were used as controls. Treatments were started immediately after operation and were continued for 6 weeks. Chronic volume-overload by shunt formation caused left ventricular dilatation and arterial enlargement proximal to the fistula. The relative wall thickness of the left ventricle was decreased, indicating eccentric cardiac hypertrophy. L-NAME elevated mean arterial blood pressure (P<0.01) and reduced the increment of cardiac output (P<0.05). L-NAME attenuated ventricular weight (P<0.01), ventricular cavity dilatation (P<0.01), and arterial enlargement (P<0.05). The re-capitulation of atrial natriuretic factor mRNA in the hypertrophied left ventricular myocardium by volume-overload was attenuated with L-NAME. In this model with chronic volume-overload, NO plays a pivotal role in the progression of cardiovascular remodeling by regulating the loading conditions of the heart. (Jpn Heart J 2003; 44: 127-137)

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Section: Discussionmentioning

confidence: 91%

Role of Nitric Oxide in the Progression of Cardiovascular Remodeling Induced by Carotid Arterio-Venous Shunt in Rabbits.

et al. 2003

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“…Indeed, in general, endothelium-mediated (drug-and shear stress-stimulated) dilation of isolated coronary arteries is reduced in hypertensive humans 11,[53][54][55][56][57] and animals, 19,21,32,36,45,51,52,[58][59][60][61][62] while the endothelium-independent vasodilatory responses to sodium nitroprusside and adenosine are often unaltered. 21,32,45,55,63 There are exceptions to these general observations 18,33,50,[63][64][65][66] and the vessel type (conduit vs resistance artery), 45,57 the mode of precontraction, 33 and the vasodilator protocol 45,56,61,67 or eliminated 58,68,69 by inhibitors of eNOS in isolated coronary vessels from hypertensive animals, suggesting that NO remains an important component of vascular function even when its bioavailability is reduced in hypertension.…”

Section: Nitric Oxide-mediated Vasomotor Function Of Isolated Coronarmentioning

confidence: 99%

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Levy

Chung²,

Kroetsch

et al. 2009

VHRM

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This review highlights a number of nitric oxide (NO)-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS) to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca 2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been studied extensively to establish mechanisms for sex differences in NO-dependent function. Genomic and nongenomic effects of estrogen on eNOS and direct and indirect antioxidant activities of estrogen are discussed as potential mechanisms of interest in coronary circulation that could have implications for sex-and estrogen status-dependent therapy for hypertension and coronary dysfunction. The current review identifies some important basic knowledge gaps and speculates on the potential clinical relevance of hypertension adaptations in factors regulating coronary NO function.

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“…9,10 In the pressure overload model by aortic banding, the impaired LV relaxation was improved effectively by antioxidant treatment, such as vitamin C or deferoxamine, indicating that excess ROS can induce LV abnormal relaxation. 11,12 To reduce ROS for cardioprotection, potassium-rich diet may be one of the candidates, because physiological increase of potassium concentration inhibited ROS formation from endothelium or white blood cells. 13 Furthermore, the cardiac hypertrophy was improved by potassium supplementation in deoxycorticosterone acetate/Na mice independent of blood pressure (BP).…”

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confidence: 99%

Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction

et al. 2006

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Abstract-Potassium supplementation has a potent protective effect against cardiovascular disease, but the precise mechanism of it against left ventricular abnormal relaxation, relatively early functional cardiac alteration in hypertensive subjects, has not been fully elucidated. In the present study, we investigated the effect of potassium against salt-induced cardiac dysfunction and the involved mechanism. Seven-to 8-week-old Dahl salt sensitive rats were fed normal diet (0.3% NaCl) or high-salt diet (8% NaCl) with or without high potassium (8% KCl) for 8 weeks. Left ventricular relaxation was evaluated by the deceleration time of early diastolic filling obtained from Doppler transmitral inflow, the slope of the pressure curve, and the time constant at the isovolumic relaxation phase. High-salt loading induced a significant elevation of blood pressure and impaired left ventricular relaxation, accompanied by augmentation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity in the cardiac tissue, measured by the lucigenin chemiluminescence method. Blood pressure lowering by hydralazine could not ameliorate NADPH oxidase activity and resulted in no improvement of left ventricular relaxation. Interestingly, although the blood pressure remained high, potassium supplementation as well as treatment with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl, a superoxide dismutase mimetic, not only reduced the elevated NADPH oxidase activity but also improved the left ventricular relaxation. In conclusion, a high-potassium diet has a potent protective effect on left ventricular active relaxation independent of blood pressure, partly through the inhibition of cardiac NADPH oxidase activity. Sufficient potassium supplementation might be an attractive strategy for cardiac protection, especially in the salt-sensitive hypertensive subjects. Key Words: sodium Ⅲ blood pressure monitoring Ⅲ cardiac function Ⅲ heart failure Ⅲ oxidative stress Ⅲ potassium H igh-salt loading on the salt-sensitive subjects results in hypertension, left ventricular (LV) hypertrophy, and hypertensive heart failure. [1][2][3][4] The hypertensive heart failure is characterized by the LV diastolic dysfunction composed of the LV abnormal relaxation and the increased LV chamber stiffness. 5 The impaired LV active relaxation, which is observed in the patients with hypertension or diabetes, 6 has been reported recently to predict a poor prognosis, 7 thus, the preservation of the LV active relaxation from early stage may be a reasonable concept.High-salt loading on the salt-sensitive model also induces overproduction of reactive oxygen species (ROS) through activation of NADPH oxidase, 8 and ROS level had a significant positive correlation with the severity of heart failure. 9,10 In the pressure overload model by aortic banding, the impaired LV relaxation was improved effectively by antioxidant treatment, such as vitamin C or deferoxamine, indicating that excess ROS can induce LV abnormal relaxation. 11,12 To reduce ROS for cardioprotec...

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Impaired Endothelium-Dependent Regulation of Ventricular Relaxation in Pressure-Overload Cardiac Hypertrophy

Cited by 56 publications

References 51 publications

Role of Nitric Oxide in the Progression of Cardiovascular Remodeling Induced by Carotid Arterio-Venous Shunt in Rabbits.

Role of Nitric Oxide in the Progression of Cardiovascular Remodeling Induced by Carotid Arterio-Venous Shunt in Rabbits.

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction

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