Systemic Endothelin Receptor Blockade Decreases Peripheral Vascular Resistance and Blood Pressure in Humans

Haynes, William G.; Ferro, Charles J.; O'kane, K. P. J.; Somerville, David; Lomax, C.; Webb, David J.

doi:10.1161/01.cir.93.10.1860

Cited by 290 publications

(183 citation statements)

References 42 publications

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“…These results are consistent with prior reports that endothelin makes important contributions to the regulation of systemic blood pressures, [6][7][8] and suggest that endothelin's contributions to altered regulation of peripheral vascular function also have an impact on elevated blood pressure particularly in DM2. The specific effect observed in diabetic subjects on pulse pressure reflects a proportionally greater reduction in systolic than diastolic pressure.…”

supporting

confidence: 92%

Blood pressure response to type A endothelin receptor antagonism in human obesity and diabetes mellitus

2006

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supporting

confidence: 92%

Blood pressure response to type A endothelin receptor antagonism in human obesity and diabetes mellitus

2006

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“…Because the venous system may contribute to the high cardiac output observed in early phases of hypertension, ET-1 may play a role at this stage of the disease. 13,22 Therefore, our finding of altered receptor profile in the saphenous veins of hypertensive patients is relevant regarding the pathogenesis of hypertension in African American patients. Results of the present study provided evidence that in addition to ET-1 expression, ET receptors are also differentially regulated in African Americans and may be important for the development and/or maintenance of hypertension in this population.…”

Section: Discussionmentioning

confidence: 88%

“…In addition to the effects of ET-1 on arteries, ET-1-mediated constriction in the venous system is enhanced in hypertensive patients. 22 Haynes et al 22 studied the responses to local infusion of ET-1 into hand veins and found that maximal contraction in response to ET-1 was significantly greater in the hypertensive group than in the normotensive group. Furthermore, ET-1 potentiated sympathetically mediated vasoconstriction in hypertensive patients, and a positive correlation was observed between ET-1-induced venoconstriction and blood pressure.…”

Section: Discussionmentioning

confidence: 99%

Saphenous Vein Endothelin System Expression and Activity in African American Patients

Grubbs

Anstadt

Ergul

2002

ATVB

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Objective-Plasma endothelin (ET)-1 levels are significantly higher in African American hypertensive patients than in white hypertensive patients. However, whether the molecular components of vascular ET-1 biosynthesis and function are altered in this population remains to be established. Accordingly, the overall goal of this study was to investigate the effects of race on vascular mRNA and protein levels of ET-converting enzyme (ECE)-1 subisoforms, ET-1, and ET receptor profiles in hypertension. Methods and Results-Saphenous vein samples were obtained from African American (nϭ13) and white (nϭ15) patients undergoing coronary artery grafting surgery. The expression of preproET-1 and of ECE-1a was upregulated Ϸ2-and 3-fold, respectively, in African Americans. In endothelium-intact vessels, the ET A expression was higher in whites. In endothelium-denuded vessels, the ET B mRNA was 3-fold higher in African Americans, suggesting that vasoconstriction-promoting ET B receptors are upregulated in this population. Vascular tissue ET-1 levels and ECE-1 activity were also augmented in African American patients. Conclusions-This study demonstrated that the biosynthetic pathway of ET-1 is activated to a higher degree and that the ET B receptor subtype expression is altered in the peripheral vasculature of African American hypertensive patients. The augmented synthesis and altered expression of ET B receptors may both contribute to the increased incidence of hypertension and related complications in this patient population. Key Words: endothelin-converting enzyme Ⅲ receptor subtype Ⅲ race Ⅲ hypertension Ⅲ gene expression T he prevalence of essential hypertension is significantly higher and the severity of cardiovascular complications is greater in the African American population than in whites. 1,2 These differences in the development and progression of hypertension in blacks have been proposed to be related to abnormal hemodynamic reactivity characterized by increased peripheral vascular resistance and diminished vasodilatation in response to environmental stress. 3 In a previous study, we found that plasma levels of the potent vasoconstrictor endothelin (ET)-1 were significantly higher in a black hypertensive group than in white hypertensive and white and black normotensive groups. 4 ET-1 acts locally in a paracrine/autocrine fashion and is predominantly secreted from the endothelial cells toward the underlying smooth muscle cells. 5 Local vascular ET-1 levels in this patient population remain unknown.The ET system consists of 3 major components: (1) ET-1, (2) ET-converting enzyme (ECE)-1, which is responsible for the biosynthesis of the active ET peptide, and (3) ET receptors, which mediate the biological effects of this peptide. Therefore, in addition to peptide levels, regulation of ECE-1 and regulation of ET receptor subtype expression in the vasculature in the setting of hypertension are equally critical. To date, there are 4 splice variants of ECE-1, with ECE-1a and ECE-1c being the most commonly expressed subisoforms...

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“…57,58 Analogous observations have been made for the control of total peripheral resistance, which is diminished by ET A and increased by ET B blockers. [60][61][62] The relative quantitative contribution of these two components to the regulation of normal BP has not been established. In essential hypertension, vasoconstriction of regional (forearm) vascular beds by ET A seems to be enhanced, 58,59 and dilation by ET B abolished or reversed.…”

Section: Endothelins and Bp Regulationmentioning

confidence: 99%

Participation of renal and circulating endothelin in salt-sensitive essential hypertension

Elijovich

Laffer

2002

J Hum Hypertens

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Salt sensitivity of blood pressure is a cardiovascular risk factor, independent of and in addition to hypertension. In essential hypertension, a conglomerate of clinical and biochemical characteristics defines a salt-sensitive phenotype. Despite extensive research on multiple natriuretic and antinatriuretic systems, there is no definitive answer yet about the major causes of salt-sensitivity, probably reflecting the complexity of saltbalance regulation. The endothelins, ubiquitous peptides first described as potent vasoconstrictors, also have vasodilator, natriuretic and antinatriuretic actions,

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Systemic Endothelin Receptor Blockade Decreases Peripheral Vascular Resistance and Blood Pressure in Humans

Cited by 290 publications

References 42 publications

Blood pressure response to type A endothelin receptor antagonism in human obesity and diabetes mellitus

Blood pressure response to type A endothelin receptor antagonism in human obesity and diabetes mellitus

Saphenous Vein Endothelin System Expression and Activity in African American Patients

Participation of renal and circulating endothelin in salt-sensitive essential hypertension

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