Vasodilator mechanisms in the coronary circulation of endothelial nitric oxide synthase-deficient mice

Lamping, Kathryn G.; Nuno, Daniel W.; Shesely, Edward G.; Maeda, Nobuyo; Faraci, Frank M.

doi:10.1152/ajpheart.2000.279.4.h1906

Cited by 88 publications

(72 citation statements)

References 40 publications

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“…44 However, in the eNOS -/-, overall total endothelium-dependent dilation of the coronary vasculature can be either unaltered, 83 reduced, 44 or eliminated 82 when compared to WT littermates. Since dilatory responses to endothelium-independent dilators in eNOS -/-are identical to those in WT in both isolated vessels 82,83 and perfused heart preparations, 40,44 these results suggest that alterations occur in the eNOS -/-as a result of changes in the activity of other endothelium-derived vasodilators to compensate for the loss of eNOS-derived NO.…”

Section: Coronary Hemodynamics and Vasomotor Activity In The Enos Knomentioning

confidence: 99%

“…The coronary vasculature of WT mice depends on NO for the majority of its overall total endothelium-dependent dilation since acute NOS inhibition eliminates most of the ACh-induced dilation in isolated preparations of the left anterior descending and left circumflex coronary arteries 82,83 and about half of the bradykinin (BK)-induced dilation in isolated heart preparations. 44 However, in the eNOS -/-, overall total endothelium-dependent dilation of the coronary vasculature can be either unaltered, 83 reduced, 44 or eliminated 82 when compared to WT littermates.…”

Section: Coronary Hemodynamics and Vasomotor Activity In The Enos Knomentioning

confidence: 99%

“…In contrast, neither inhibitor affected the responses in WT vessels. 83 This suggests that nNOS-derived NO and prostacyclin may compensate for the loss of eNOS in eNOS -/-to preserve coronary artery endothelium-dependent dilation. It is also possible that upregulation of cytochrome-P450 metabolites may be responsible for some of the compensatory endothelium-dependent dilation observed in the eNOS -/-coronary vasculature.…”

Section: Coronary Hemodynamics and Vasomotor Activity In The Enos Knomentioning

confidence: 99%

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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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Section: Coronary Hemodynamics and Vasomotor Activity In The Enos Knomentioning

confidence: 99%

Section: Coronary Hemodynamics and Vasomotor Activity In The Enos Knomentioning

confidence: 99%

Section: Coronary Hemodynamics and Vasomotor Activity In The Enos Knomentioning

confidence: 99%

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Nitric oxide and coronary vascular endothelium adaptations in hypertension

Levy

Chung²,

Kroetsch

et al. 2009

VHRM

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“…32 In each case the compensatory PG dilator was derived from the endothelium. 31,32 These data suggest that certain vessels have the ability to compensate for the loss of one endothelium-dependent vasodilator mechanism by upregulating an alternative endothelium-dependent dilator system (EDHF or prostaglandins).…”

Section: Hatoum Et Al Novel Nonendothelial Release Of Pgd 2 2359mentioning

confidence: 99%

“…9,30 Lamping et al showed that in coronary arteries from wild-type mice, dilation to Ach is mediated primarily by NO, whereas in endothelial NO synthase knockout mice, the dilation is dependent on activity of neuronal nitric oxide synthase and COX. 31 Sun et al showed that flow-induced dilation is mediated by both endothelial NO and prostaglandins in skeletal muscle arterioles from wild-type mice, but is mediated exclusively by prostaglandins in male endothelial NO synthase knockout mice. 32 In each case the compensatory PG dilator was derived from the endothelium.…”

Section: Hatoum Et Al Novel Nonendothelial Release Of Pgd 2 2359mentioning

confidence: 99%

Novel Mechanism of Vasodilation in Inflammatory Bowel Disease

Hatoum

Gauthier

Binion

et al. 2005

ATVB

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Objective-Endothelium-dependent dilation to acetylcholine (Ach) is reduced in mucosal arterioles from patients with inflammatory bowel disease (IBD). The contributions of both nitric oxide (NO) and endothelial-derived hyperpolarizing factor (EDHF) are decreased. We hypothesized that the remaining dilation results from products of cyclooxygenase. Methods and Results-High-performance liquid chromatography (HPLC) was used to isolate eicosanoid vasodilator products and videomicroscopy was used to examine vasomotor responses in human mucosal arterioles from subjects with or without IBD undergoing bowel resection surgeries. In subjects without IBD, Ach constricted (Ϫ52%Ϯ10%) arterioles devoid of endothelium. Indomethacin (INDO) (cyclooxygenase inhibitor) had no effect. In contrast, Ach dose-dependently dilated both intact and endothelial denuded arterioles from patients with IBD. The dilation was converted to constriction by INDO (Ϫ54%Ϯ9%; PϽ0.05 versus non-IBD) or by BWA868C (PGD 2 receptor antagonist). Only in arterioles from subjects with IBD did Ach produce an arachidonic acid metabolite that comigrated on HPLC with PG D 2 (PGD 2 ). Exogenous PGD 2 dilated (maxϭ66%Ϯ4%) IBD arterioles. Conclusion-In arterioles from IBD patients, Ach-mediated dilation shifts from endothelial production of NO and EDHF to nonendothelial generation of a PG, likely PGD 2 . This is a novel dilator mechanism arising from nonendothelial vascular tissue that compensates for loss of endothelium-dependent dilation. PGD 2 appears to be important in regulating mucosal blood flow in patients with IBD, implicating potentially detrimental effects from nonsteroidal antiinflammatory drugs. Key Words: cyclooxygenase Ⅲ inflammatory bowel disease Ⅲ microcirculation Ⅲ prostaglandin Ⅲ vasodilation E ndothelium-dependent vasorelaxation plays a critical role in regulating tissue perfusion. 1 Impaired vasorelaxation is a key feature of microvascular dysfunction that contributes to the pathophysiology of diabetes mellitus, hyperlipidemia, and atherosclerosis. 2,3 A new association of microvascular dysfunction with clinical inflammatory bowel disease (IBD) (Crohn disease, ulcerative colitis) has been made. 4 IBD is characterized by refractory, poorly healing mucosal ulcerations, and impaired endothelium-mediated vasorelaxation. 4,5 Using in vitro dimension measurements of cannulated 50 to 200 m arterioles, we have demonstrated that normal intestinal microvessels dilate in response to the classic endothelium-dependent agonist, acetylcholine (Ach). 4 After inhibiting nitric oxide (NO) synthase, cyclooxygenase (COX), and hyperpolarization mechanisms, or after endothelial denudation, constriction was observed. Microvessels isolated from chronically inflamed IBD tissue demonstrated loss of NO-mediated and hyperpolarization-mediated vasodilation in response to Ach. However, in contrast to vessels from subjects without IBD or from uninvolved segments of bowel from patients with IBD, arterioles from active IBD segments had attenuated dilation to Ach that was independ...

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Redox Regulation of the Microcirculation

Kadlec

Gutterman

2019

Comprehensive Physiology

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The microcirculation maintains tissue homeostasis through local regulation of blood flow and oxygen delivery. Perturbations in microvascular function are characteristic of several diseases and may be early indicators of pathological changes in the cardiovascular system and in parenchymal tissue function. These changes are often mediated by various reactive oxygen species and linked to disruptions in pathways such as vasodilation or angiogenesis. This overview compiles recent advances relating to redox regulation of the microcirculation by adopting both cellular and functional perspectives. Findings from a variety of vascular beds and models are integrated to describe common effects of different reactive species on microvascular function. Gaps in understanding and areas for further research are outlined.

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Vasodilator mechanisms in the coronary circulation of endothelial nitric oxide synthase-deficient mice

Cited by 88 publications

References 40 publications

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Novel Mechanism of Vasodilation in Inflammatory Bowel Disease

Redox Regulation of the Microcirculation

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