Induction of endothelin-1 expression by oxidative stress in vascular smooth muscle cells

Ruef, Johannes; Moser, Martin; Kübler, W.; Bode, Christoph

doi:10.1016/s1054-8807(01)00095-3

Cited by 87 publications

(63 citation statements)

References 40 publications

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“…Recently, it has been reported that Ang II stimulation evokes expression of ET-1 in adventitial fibroblasts contributes to type I procollagen expression through activation of ET A receptors, suggesting a functional role for adventitial ET-1 release in the regulation of the extracellular matrix [15] . Expression of ET-1 in adventitial fibroblasts is mediated by ·O 2 - [16] , consistent with the findings in many different cell types [17] , including VSM [18,19] . However, the mechanisms of oxidative stress regulating ET-1 production are still unclear.…”

Section: Perivascular Fibroblasts: Source Of Ros and Regulation Of Vasupporting

confidence: 89%

New perspectives on vascular wall signaling: role of perivascular adipocytes and fibroblasts

Kwan

Hsieh

et al. 2010

Acta Pharmacol Sin

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Section: Perivascular Fibroblasts: Source Of Ros and Regulation Of Vasupporting

confidence: 89%

New perspectives on vascular wall signaling: role of perivascular adipocytes and fibroblasts

Kwan

Hsieh

et al. 2010

Acta Pharmacol Sin

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“…40,41 Whereas ET-1 can increase oxidative stress, there are a number of reports that reactive oxygen species can increase ET-1 production in cultured endothelial cells and vascular smooth muscle cells. [42][43][44][45] Hydrogen peroxide and superoxide can increase ET-1 synthesis, and 8-iso prostaglandin F2ϰ, a product formed by free radical catalyzed lipid peroxidation, also can have similar effects. 42 The relevance of these observations is unclear given that Saito et al observed contrasting findings that hydrogen peroxide actually decreases ET-1 mRNA and protein synthesis in endothelial cells.…”

Section: Et-1 and Oxidative Stressmentioning

confidence: 99%

Endothelin, Angiotensin, and Oxidative Stress in Hypertension

Pollock

2005

Hypertension

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E ndothelin (ET)-1 is a potent vasoconstrictor and mitogen, and because of these properties, it is thought to play a role in the development of hypertension. 1,2 The vascular endothelium is a major source of ET-1 production, although a variety of other cell types also have been shown to synthesize and release ET-1. ET-1 is believed to act in a paracrine manner on ET A and ET B receptors on smooth muscle, which mediate contraction, cell proliferation, and hypertrophy. Activation of ET B receptors on endothelial cells stimulates the production of prostacyclin and nitric oxide to induce vasorelaxation and inhibition of sodium transport in renal tubules. Given these properties, considerable attention has been paid to the mechanisms of ET-1 action as it relates to the renal control of blood pressure and the pathogenesis of salt-dependent hypertension. Renal ET synthesis is increased in experimental animals maintained on a high-salt diet and ET A receptor antagonists lower arterial pressure primarily in salt-dependent models of hypertension. 1,2 For the past 30 to 40 years, the actions of angiotensin (Ang) II has been arguably the most widely investigated factor in hypertension research. Although physiology textbooks agree on the major actions of Ang II, eg, vasoconstriction and release of aldosterone, recent attention has focused on its ability to stimulate the synthesis of ET-1, 3-5 as well as reactive oxygen species. 6 There are many reactive oxygen species such as superoxide, hydroxyl radical, and hydrogen peroxide that are produced by all cell types and can have profound effects on the vascular system to impact blood pressure regulation. Most recent attention has been paid to the role of superoxide. There are many enzymatic sources of superoxide including NADPH oxidase, xanthine oxidase, nitric oxide synthase, and cytochrome P450. The focus of the current review, however, is be on the interaction between the 2 peptide systems, ET-1 and Ang II, as they relate to oxidative stress. ET-1 in Ang II Hypertension ET-1 and Oxidative StressThe clinical significance of oxidative stress and its role in hypertension was recently reviewed by Touyz, 18 and so the current discussion is limited to the interaction between ET-1, Ang II, and superoxide.Studies from Ortiz et al have shown that the slow pressor response to Ang II is associated with increases in ET, as well as isoprostanes, a marker of lipid oxidation and an index of oxidative stress. 9 These effects could be prevented with bosentan, suggesting a role for ET in mediating the increase in oxidative stress in this model. They went on to demonstrate that antioxidant treatment with the superoxide dismutase mimetic, tempol, or the combination of vitamins C and E reduced Ang II-induced changes in ET expression. 14 Acute administration of tempol also has antihypertensive effects in rats chronically infused with Ang II. 15 Long-term treatment with tempol will lower arterial pressure in several models of hypertension associated with increases in ET production, including chroni...

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“…10 -12 Apart from inducing vasoconstriction, ET-1 activates vascular NADPH oxidase, leading to an increase in oxidative stress through enhanced reactive oxygen species (ROS) production. 13,14 Because oxidative stress is generally increased in hypertension and plays a pathogenic role in the development and progression of cardiovascular disease, we hypothesized that enhanced formation of ROS contributes to the sunitinib-induced cardiovascular adverse effects. 15 To further explore the cardiovascular adverse effects of sunitinib, we performed detailed studies in chronically instrumented awake swine.…”

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confidence: 99%

Sunitinib-Induced Systemic Vasoconstriction in Swine Is Endothelin Mediated and Does Not Involve Nitric Oxide or Oxidative Stress

et al. 2012

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Abstract-Angiogenesis inhibition with agents targeting tyrosine kinases of vascular endothelial growth factor receptors is an established anticancer treatment, but is, unfortunately, frequently accompanied by systemic hypertension and cardiac toxicity. Whether vascular endothelial growth factor receptor antagonism also has adverse effects on the pulmonary and coronary circulations is presently unknown. In chronically instrumented awake swine, the effects of the vascular endothelial growth factor receptor antagonist sunitinib on the systemic, pulmonary, and coronary circulation were studied. One week after sunitinib (50 mg PO daily), mean aortic blood pressure (MABP) had increased from 83Ϯ5 mm Hg at baseline to 97Ϯ6 mm Hg (PϽ0.05) because of a 57Ϯ20% increase in systemic vascular resistance as cardiac output decreased. In contrast, sunitinib had no discernible effects on pulmonary and coronary hemodynamics or cardiac function. We subsequently investigated the mechanisms underlying the sunitinib-induced systemic hypertension. Intravenous administration of NO synthase inhibitor N G -nitro-L-arginine increased MABP by 24Ϯ1 mm Hg under baseline conditions, whereas it increased MABP even further after sunitinib administration (32Ϯ3 mm Hg; PϽ0.05). Reactive oxygen species scavenging with a mixture of antioxidants lowered MABP by 13Ϯ2 mm Hg before but only by 5Ϯ2 mm Hg (PϽ0.05) after sunitinib administration. However, intravenous administration of the dual endothelin A/endothelin B receptor blocker tezosentan, which did not lower MABP at baseline, completely reversed MABP to presunitinib values. These findings indicate that sunitinib produces vasoconstriction selectively in the systemic vascular bed, without affecting pulmonary or coronary circulations. The sunitinib-mediated systemic hypertension is principally attributed to an increased vasoconstrictor influence of endothelin, with no apparent contributions of a loss of NO bioavailability or increased oxidative stress. (Hypertension. 2012;59:151-157.) Key Words: endothelin 1 Ⅲ hypertension Ⅲ oxidative stress Ⅲ pulmonary hypertension Ⅲ vascular endothelial growth factor A ngiogenesis inhibition, by targeting the tyrosine kinases of the vascular endothelial growth factor (VEGF) receptors (VEGFRs), has become an established treatment of several tumor types. This therapy is associated with adverse effects, including the development of hypertension and cardiac and renal toxicity. 1 Hypertension has been reported in Յ60% of patients treated with sunitinib, an orally active multitarget receptor tyrosine kinase inhibitor (RTKI), targeting, among others, the VEGFR-1 and -2, which is used as first-line treatment of metastatic renal cell carcinoma or imatinib-resistant gastrointestinal stromal tumors. 1 In addition, impaired cardiac function, as reflected by a decrease in left ventricular ejection fraction of 10% to 15%, has been observed in Յ28% of patients treated with sunitinib. 2 Angina pectoris and increased levels of biomarkers reflecting ischemic myocardial damage may als...

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Induction of endothelin-1 expression by oxidative stress in vascular smooth muscle cells

Cited by 87 publications

References 40 publications

New perspectives on vascular wall signaling: role of perivascular adipocytes and fibroblasts

New perspectives on vascular wall signaling: role of perivascular adipocytes and fibroblasts

Endothelin, Angiotensin, and Oxidative Stress in Hypertension

Sunitinib-Induced Systemic Vasoconstriction in Swine Is Endothelin Mediated and Does Not Involve Nitric Oxide or Oxidative Stress

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