Expression of a recombinant preproendothelin-1 gene in arteries stimulates vascular contractility

Schott, E.; Tostes, Rita C.; H, San; Paul, Marilyn S.; Webb, R. Clinton; Nabel, Elizabeth G.

doi:10.1152/ajpheart.1997.272.5.h2385

Cited by 3 publications

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“…11 Angiotensin (Ang) II induces mRNA and protein expression of endothelin (ET)-1, a strong vasoconstrictor 15 and mitogen, 16 in vitro 15,17,18 and in the kidney and vasculature in vivo. 19,20 Interestingly, ET-1 increases the formation of Ang II from Ang I, [21][22][23] suggesting modulation of ACE activity. ET-1 is also involved in lipid metabolism 24,25 and has been implicated in the pathogenesis of obesity-associated hypertension.…”

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confidence: 97%

Obesity Is Associated With Tissue-Specific Activation of Renal Angiotensin-Converting Enzyme In Vivo

et al. 2000

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Abstract-In the C57BL/6J mice model, we investigated whether obesity affects the function or expression of components of the tissue renin-angiotensin system and whether endothelin (ET)-1 contributes to these changes. ACE activity (nmol ⅐ L His-Leu ⅐ mg protein Ϫ1 ) was measured in lung, kidney, and liver in control (receiving standard chow) and obese animals treated for 30 weeks with a high-fat, low cholesterol diet alone or in combination with LU135252, an orally active ET A receptor antagonist. ACE mRNA expression was measured in the kidney, and the effects of LU135252 on purified human ACE were determined. Aortic and renal tissue ET-1 protein content was measured, and the vascular contractility to angiotensin II was assessed. Obesity was associated with a tissue-specific increase in ACE activity in the kidney (55Ϯ4 versus 33Ϯ3 nmol/L) but not in the lung (34Ϯ2 versus 32Ϯ2 nmol/L). Long-term LU135252 treatment completely prevented this activation (13.3Ϯ0.3 versus 55Ϯ4 nmol/L, PϽ0.05) independent of ACE mRNA expression, body weight, or renal ET-1 protein but did not affect pulmonary or hepatic ACE activity. Obesity potentiated contractions in response to angiotensin II in the aorta (from 6Ϯ2% to 33Ϯ5% KCl) but not in the carotid artery (4Ϯ1% to 3.6Ϯ1% KCl), an effect that was completely prevented with LU135252 treatment (6Ϯ0.4% versus 33Ϯ5% KCl). No effect of LU135252 on purified ACE was observed. Thus, obesity is associated with the activation of renal ACE in vivo independent of its mRNA expression and enhanced vascular contractility to angiotensin II. These effects are regulated by ET in an organ-specific manner, providing novel mechanisms by which ET antagonists may exert organ protection.

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confidence: 97%

Obesity Is Associated With Tissue-Specific Activation of Renal Angiotensin-Converting Enzyme In Vivo

et al. 2000

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“…Endothelin infusion increases coronary vascular resistance and decreases cardiac output and heart rate [24,73]. After transfection with the preproET-1 gene, contraction of porcine arteries in vivo is augmented due to increased sensitivity to Ang I, implying a role for ET-1 in the pathogenesis of cardiovascular disease [74]. Increased ET levels are reported in heart failure, an important constituent of hypertensive end-organ damage, suggesting a possible role for ET in this disease [75].…”

Section: Heart Failurementioning

confidence: 99%

A role for endothelin in the pathogenesis of hypertension: Fact or fiction?

Pinto‐Sietsma

Paul

1998

Kidney International

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A role for endothelin in the pathogenesis of hypertension: Fact or fiction? Endothelin-1 (ET-1) was discovered 10 years ago. Because it is one of the most potent vasoconstrictors in vivo, a pathophysiological role for the peptide as a mediator of hypertension has been postulated. Several clinical studies, however, have been unable to identify elevated ET levels in the plasma of hypertensive patients, suggesting that it does not play a prominent role in this disease. More recently, evidence has been presented that ETs act predominantly at the autocrine/paracrine level and that measurements of plasma levels can give only an indirect view of the activity of the system. In addition, transgenic technology has uncovered new actions of the peptide systems in recent years, which point to a key function of the system in prenatal development. Moreover, investigation of conditions associated with hypertensive end-organ damage, such as chronic renal failure, has led to a re-evaluation of the role of the ET system in hypertension. This article discusses this recent evidence and defines the exact role of the ET system in hypertension and hypertensive end-organ damage.

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Virally Mediated Gene Transfer to the Vasculature

Gunnett

Heistad

2002

Microcirculation

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Gene transfer technology provides valuable tools for the study of vascular biology. By using gene transfer, effects of specific gene products can be evaluated in a highly selective manner. In recent years, techniques used for gene transfer have been adapted for applications to blood vessels, including microvessels, both in vitro and in vivo. The purpose of this review is to provide a survey of published work in this field of investigation and to discuss advantages and limitations of current methods used for gene transfer to the vasculature.

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Expression of a recombinant preproendothelin-1 gene in arteries stimulates vascular contractility

Cited by 3 publications

References 0 publications

Obesity Is Associated With Tissue-Specific Activation of Renal Angiotensin-Converting Enzyme In Vivo

Obesity Is Associated With Tissue-Specific Activation of Renal Angiotensin-Converting Enzyme In Vivo

A role for endothelin in the pathogenesis of hypertension: Fact or fiction?

Virally Mediated Gene Transfer to the Vasculature

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