Antihypertensive therapy augments endothelium-dependent relaxations in coronary arteries of spontaneously hypertensive rats.

Tschudi, Marcel R.; Criscione, Leoluca; Novosel, Dragutin; Pfeiffer, Karl P.; Lüscher, Thomas F.

doi:10.1161/01.cir.89.5.2212

Cited by 120 publications

(65 citation statements)

References 39 publications

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“…48 Other studies have documented an inhibitory effect of AT 1 receptor activation on NO synthetase mRNA and restoration of mRNA expression and NO-mediated vasorelaxation with blockade of AT 1 receptors. 49,50 These studies provide a conceptual basis for the relationship between increased AT 1 expression and loss of NO-dependent relaxation in the presence of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Yang

Phillips

Mohuczy

et al. 1998

ATVB

121

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Abstract-Angiotensin II (Ang II) promotes vascular smooth muscle growth and may be involved in the initiation and progression of atherosclerosis. To examine whether Ang II receptor expression in vascular tissues is altered in atherosclerosis, male New Zealand White rabbits were fed a high-cholesterol diet (1% cholesterolϩ4% coconut oil mixed with regular chow; hypercholesterolemic group, nϭ12) or regular chow (control group, nϭ8) for 10 weeks. At the end of this period, the serum cholesterol level in the rabbits fed the high-cholesterol diet was higher than that in the control group (3616Ϯ144 versus 30Ϯ1 mg/dL, PϽ0.001). There was no atherosclerosis in the aortas of the control group, whereas 51Ϯ6% of the aorta was covered with atherosclerosis in the hypercholesterolemic group. Total Ang II receptor expression in the atherosclerotic aortic tissues was increased 5-fold in the hypercholesterolemic rabbits (292Ϯ28 versus 51Ϯ32 fmol/mg tissue, meanϮSE, PϽ0.001), and the increased Ang II receptor expression was entirely due to enhanced Ang II type 1 (AT 1 ) receptor expression (289Ϯ38 versus 38Ϯ18 fmol/mg, PϽ0.001), as Ang II type 2 receptor expression was unaltered (7Ϯ5 versus 3Ϯ2 fmol/mg, PϭNS). AT 1 receptors were localized primarily in the media and to some extent in the intima of the atherosclerotic aorta, as determined by immunohistochemistry with specific monoclonal and polyclonal AT 1 receptor antibodies. Increased synthesis of AT 1 receptor mRNA in atherosclerotic tissues was confirmed by reverse transcription-polymerase chain reaction. To evaluate the functional significance of increased AT 1 receptor expression, the constrictor response of aortic rings to Ang II was examined and found to be markedly enhanced in atherosclerotic aortic rings (PϽ0.01 versus control aortic rings). The endotheliumdependent relaxation of aortic rings from hypercholesterolemic rabbits was markedly attenuated (PϽ0.001). This study shows that hypercholesterolemia in rabbits results in atherosclerosis, loss of endothelium-dependent relaxation, and increased Ang II receptor (entirely AT 1 receptor) expression in aortic tissues, which may result in altered vasoreactivity.

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Section: Discussionmentioning

confidence: 99%

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Yang

Phillips

Mohuczy

et al. 1998

ATVB

121

View full text Add to dashboard Cite

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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. In isolated pressurized coronary microvessels it was observed that removal of the endothelium increased the amount of myogenic constriction to a greater extent in SHR than in WKY over a wide pressure range.…”

Section: Nitric Oxide-mediated Vasomotor Function Of Isolated Coronarmentioning

confidence: 97%

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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“…104,[203][204][205][206][207][208][209] Surprisingly and in contrast to animal experiments, antihypertensive therapy cannot consistently restore impaired endothelium-dependent vasodilation in patients with arterial hypertension. [43][44][45][46][47][48][49][50][51][52][53]210 However, depending on the antihypertensive drug and its pharmacological profile, improvements in endothelium-dependent vasodilation can be achieved (Table 1).…”

Section: Effects Of Antihypertensive Therapy On Endothelial Function mentioning

confidence: 99%

Working under pressure: the vascular endothelium in arterial hypertension

et al. 2000

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The vascular endothelium synthesizes and releases a spectrum of vasoactive substances like nitric oxide (NO) and endothelin (ET). In hypertension, the delicate balance of endothelium-derived factors is disturbed. ET acts as the natural counterpart to endothelium-derived NO, which exerts vasodilating, antithrombotic, and antiproliferative effects, and inhibits leukocyte-adhesion to the vascular wall. Besides its blood pressure rising effect also in man, ET induces vascular and myocardial hypertrophy, which are independent risk factors for cardiovascular morbidity and mortality. The derangement of endothelial function in hypertension is likely to be caused in part by genetic factors, but also due to elevated blood pressure itself. Due to its position between blood pressure and smooth muscle cells responsible for peripheral resistance, the endothelium is thought to be both target and mediator of arterial hypertension. Oxi-

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Antihypertensive therapy augments endothelium-dependent relaxations in coronary arteries of spontaneously hypertensive rats.

Cited by 120 publications

References 39 publications

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Working under pressure: the vascular endothelium in arterial hypertension

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