Angiotensin II Activates Endothelial Constitutive Nitric Oxide Synthase via AT1 Receptors.

Saito, Shuichi; Hirata, Yukio; Emori, Toshiaki; Imai, Taihei; Marumo, Fumiaki

doi:10.1291/hypres.19.201

Cited by 74 publications

(57 citation statements)

References 23 publications

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“…Studies on bovine vascular endothelial cells and rat aortic endothelial cells have demonstrated that ANG II can increase the expression and activity of endothelial nitric oxide synthase, leading to increased production of NO (4,32,34). ANG II also increases the expression of cyclooxygenase-2 in human vascular endothelial cells (20), rat ventricular cardiomyocytes (33), and rat vascular smooth muscle cells (31), stimulating production of the vasodilator prostaglandins PGI 2 and PGE 2 (2,33).…”

Section: Discussionmentioning

confidence: 99%

Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation

Drenjančević-Perić

Lombard

2004

American Journal of Physiology-Heart and Circulatory Physiology

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Drenjancevic-Peric, Ines, and Julian H. Lombard. Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation. Am J Physiol Heart Circ Physiol 287: H957-H962, 2004. First published March 18, 2004 10.1152/ajpheart.01087.2003.-To evaluate the potential role of impaired reninangiotensin system (RAS) function in contributing to reduced vascular relaxation in Dahl salt-sensitive (S) rats, responses to ACh (10 Ϫ6 mol/l) and hypoxia (PO2 reduction to 40 -45 mmHg) were determined in isolated middle cerebral arteries of Dahl S rats, Brown Norway (BN) rats, and consomic rats having chromosome 13 (containing the renin gene) or chromosome 16 of the BN rat substituted into the Dahl S genetic background (SS-13 BN and SS-16 BN , respectively). Arteries of BN rats on a low-salt (LS) diet (0.4% NaCl) dilated in response to ACh and hypoxia, whereas dilation in response to these stimuli was absent in Dahl S rats on LS diet. Vasodilation to ACh and hypoxia was restored in SS-13 BN rats on an LS diet but not in SS-16 BN rats. High-salt diet (4% NaCl), to suppress ANG II, eliminated vasodilation to hypoxia and ACh in BN and in SS-13 BN rats. Treatment of SS-13 BN rats with the AT1 receptor antagonist losartan also eliminated the restored vasodilation in response to ACh and hypoxia. These studies suggest that restoration of normal RAS regulation in SS-13 BN consomic rats restores vascular relaxation mechanisms that are impaired in Dahl S rats.hypertension; vascular smooth muscle; renin-angiotensin system; physiological genomics THE RAT IS A WELL-ESTABLISHED experimental model for studies of physiological control mechanisms and pathophysiological conditions, including hypertension. Vascular control mechanisms have been studied extensively in resistance arteries and microvessels of several commonly used inbred and outbred strains of normotensive rats, and in many rat models of hypertension. However, it is now known that different strains of rats exhibit substantial differences in physiological control mechanisms, and these differences can provide valuable information about the genetic basis for various pathophysiological conditions. For example, resistance to global myocardial ischemia is twofold greater in hearts of Brown Norway (BN) rats compared with those of Dahl salt-sensitive (Dahl S) rats (3). In that study, infarct size and postischemic leakage of lactate dehydrogenase were significantly less, and recovery of coronary flow rate and rate-pressure product were significantly faster in BN vs. Dahl S rats. Other studies have shown that BN rats exhibit normal regulation of the renin-angiotensin system (RAS) when dietary salt intake is changed, whereas Dahl S rats have an impaired ability to regulate their RAS (1, 6).Although genetic linkage analysis of blood pressure differences among various strains of rats provides valuable clues regarding the possible role of different genes in contributing to the development and maintenance of hypertension (7,22,25,35), simplified models such as co...

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Section: Discussionmentioning

confidence: 99%

Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation

Drenjančević-Perić

Lombard

2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…Lack of significant difference in the hypertensive phenotypes of rgs2 heterozygous versus homozygous nulls could result from stimulation of endothelial production of NO or other vasodilatory factors by angiotensin II (39)(40)(41)(42). According to this model, an initial response to angiotensin II would be more robust in rgs2 homozygous nulls than in heterozygous nulls, but blood pressure would not be higher in rgs2 homozygous nulls because they would produce more NO or other vasodilatory factors as a counterbalancing mechanism.…”

Section: Discussionmentioning

confidence: 99%

Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice

Heximer¹,

Knutsen²,

Sun³

et al. 2003

J. Clin. Invest.

244

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“…This vasoconstriction is partly inhibited by Ang II-mediated release of NO from the endothelium. 47,48 Because individuals with the ACE D allele have higher plasma and tissue ACE concentrations, we hypothesized that the D allele of the ACE gene, by increasing local Ang II generation and decreasing bradykinin activity, may modulate vascular tone. 10,49 In the present study, we found no difference in endothelial function in the sedentary subjects according to ACE genotypes, as has been found in other studies.…”

Section: Ace Gene Polymorphism and Endothelial Functionmentioning

confidence: 99%

Improved Endothelium Dependent Vasodilation in Endurance Athletes and Its Relation With ACE I/D Polymorphism

Tanrıverdi

Evrengül

Tanrıverdi

et al. 2005

Circ J

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he vascular endothelium plays an important role in the regulation of vascular tone and the maintenance of cardiovascular homeostasis. 1 Importantly, endothelial dysfunction, particularly impaired endotheliumdependent vasodilation, has been linked to the pathogenesis of atherosclerotic vascular disease and acute cardiovascular events. 2 Indeed, reduced endothelial vasodilatory function occurs early in atherogenesis before histological and angiographic evidence. 3,4 Epidemiologic studies have shown that high levels of physical activity and cardiorespiratory fitness reduce cardiovascular morbidity and mortality in the general population, including healthy subjects. 5,6 It is clinically important to select the appropriate kind of exercise. Regular aerobic exercise is associated with beneficial changes in blood pressure, lipid metabolism, glucose metabolism, neurohormonal factors, body weight, and shear stress. 7,8 Although the mechanism of improvement in endothelial function during exercise has not been fully clarified, it is thought that nitric oxide (NO) production is increased by up-regulation of endothelial NO synthase gene expression and vascular endothelial growth factor-induced angiogenesis, as well as decreased NO inactivation with augmented antioxidants, Circulation Journal Vol. 69, September 2005 such as superoxide dismutase and glutathione peroxidase, and attenuation of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity, all leading to an increase in NO bioavailability. 9 Polymorphisms of the angiotensin converting enzyme (ACE) gene, located on chromosome 17, have been found and the polymorphism is characterized by the presence (insertion (I)) or absence (deletion (D)) of a 287-base-pair alu repeat within intron 16. The presence of the D allele has been associated with higher concentrations of circulating and tissue ACE. Increased ACE activity might lead to high Angiotensin II (Ang II) concentrations. 10 Of the several candidate genes for endothelial dysfunction, the ACE gene appears to be a likely one because (1) it is anchored via its carboxyl terminus to the endoluminal side of the endothelial cell plasma membrane, from where it can be released in the bloodstream, 11,12 and (2) the increased plasma ACE activity found in subjects with the D allele could decrease bradykinin bioactivity with ensuing blunting of receptormediated release of NO. 13 Furthermore, even though the literature is variable on whether Ang II effects are increased in subjects with the D allele, 14,15 enhanced Ang II production can increase the concentrations of superoxide through increased activity of NADH/NADPH oxidase activity 16 and thus lower the bioactivity of NO. 17 The balance of vasodilators and vasoconstrictors also plays an important role in the physiologic regulation of vascular tone; 18 However, it is not clear whether the ACE genotype can modify the endothelial response to exercise in athletes.The aim of this study was to investigate the relationship between the...

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Angiotensin II Activates Endothelial Constitutive Nitric Oxide Synthase via AT1 Receptors.

Cited by 74 publications

References 23 publications

Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation

Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation

Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice

Improved Endothelium Dependent Vasodilation in Endurance Athletes and Its Relation With ACE I/D Polymorphism

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