Endothelin Mediates Some of the Renal Actions of Acutely Administered Angiotensin II

Riggleman, Amy; Harvey, Jeff; Baylis, Chris

doi:10.1161/01.hyp.38.1.105

Cited by 37 publications

(28 citation statements)

References 34 publications

(37 reference statements)

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“…It is evident therefore that adrenomedullin is released from endothelial cells in response to two potent vasoconstrictors, angiotensin-II and endothelin-1. In that some actions of angiotensin-II are via stimulation of endothelin-1 (Riggleman et al 2001, Pollock 2005, it is possible that the adrenomedullin response to angiotensin-II observed in the present study resulted from augmented endothelin-1 production in endothelial cells.…”

Section: Discussionmentioning

confidence: 73%

Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II

Lj¹,

Rait²,

Nicholls³

et al. 2006

Journal of Endocrinology

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It is well documented that there are gender differences in the incidence and patterns of cardiovascular diseases but the reasons are unclear. Sex steroids may modulate the behaviour of vascular endothelial cells, which in turn act by paracrine processes to alter adjacent vascular smooth muscle activity. We hypothesised that the sex steroids alter the percentage of vascular endothelial cells that secrete the vasodilator peptide, adrenomedullin and modify the adrenomedullin-stimulating action of angiotensin-II. The percentage of adrenomedullinsecreting human aortic endothelial cells was determined using the cell immunoblot method. Cells were incubated with selected concentrations of angiotensin-II, oestradiol and testosterone alone and sex steroids in combination with angiotensin-II. Adrenomedullin mRNA expression in endothelial cells was quantified by real-time PCR. It was observed that at 4 h, angiotensin-II increased the percentage of adrenomedullin-secreting cells in a concentration-dependent manner. Testosterone at physiological concentrations was observed to increase the number of adrenomedullin-secreting cells whilst oestradiol had no effect. Addition of testosterone to angiotensin-II resulted in less than additive increases in the number of cells secreting adrenomedullin. Oestradiol reduced the angiotensin-II-induced increase in adrenomedullinsecreting cells. Adrenomedullin mRNA expression was significantly increased by testosterone and there was also a trend for an increase in adrenomedullin mRNA expression, which occurred when cells were incubated with angiotensin-II. Our results point to a complex interplay between the sex steroids and angiotensin-II in regulating adrenomedullin production by human endothelial cells, which may contribute to gender-related differences in vascular disease in humans.

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Section: Discussionmentioning

confidence: 73%

Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II

Lj¹,

Rait²,

Nicholls³

et al. 2006

Journal of Endocrinology

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“…Although Ang II stimulates ET-1 synthesis in endothelial cells, several hours are required for this effect, 3 whereas ET A blockade blunts very rapidly the systemic or renal actions of Ang II in our healthy humans as well as in rats. [12][13][14][15][16] However, release of ET-1 takes place within minutes from in vitro vessels 3,17 or human vascular cultured cells exposed to Ang II, 33 implying that preformed ET-1 is stored in cells and that its release may be Ang II-dependent. 15 Such a mechanism cannot, therefore, be excluded in our human model despite no change in plasma ET-1 levels.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15][16] However, release of ET-1 takes place within minutes from in vitro vessels 3,17 or human vascular cultured cells exposed to Ang II, 33 implying that preformed ET-1 is stored in cells and that its release may be Ang II-dependent. 15 Such a mechanism cannot, therefore, be excluded in our human model despite no change in plasma ET-1 levels. In fact, plasma ET-1 may not reflect an increase in its tissue concentration due to the preferential release of peptide on basolateral side of endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…9 -11 Furthermore, ET-1 participates in the acute pressor effects of exogenous Ang II 12,13 and partly mediates the vasoconstriction from exogenous Ang II in different vascular beds, including kidney. 14,15 Interestingly, studies in rats have shown that such Ang II-ET-1 interaction may be sodium-dependent, because under elevated sodium intake, ET A blockade inhibited Ang II hypertension much more than under sodium restriction. 16 Ang II also stimulates both ET-1 synthesis and release, 3,4,17 whereas ET-1 enhances the pressor action of Ang II.…”

mentioning

confidence: 99%

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Endothelin-A Receptors Mediate Renal Hemodynamic Effects of Exogenous Angiotensin II in Humans

Montanari

Carra

et al. 2003

Hypertension

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Abstract-To investigate whether endothelin-A receptors mediate hemodynamic changes caused by exogenous Angiotensin II in humans, 7 healthy volunteers on a 250-mmol sodium diet underwent 3 separate p-aminohippurate and inulin-based renal hemodynamic studies. In 2 studies, Angiotensin II (increasing rates of 0.625, 1.25, and 2.5 ng/kg per minute, each for 30 minutes) was infused either alone or combined with endothelin-A blocker, BQ123, 0.4 nmol/kg per minute. A third infusion of BQ123 alone was not followed by any change. Key Words: receptors, endothelin Ⅲ angiotensin II Ⅲ kidney Ⅲ hemodynamics Ⅲ human A ngiotensin II (Ang II), a potent endogenous vasoconstricting and sodium-retaining peptide, plays a key role in the regulation of renal function and arterial pressure, 1,2 mostly by activating Ang II-type 1 (AT1) receptors, which leads to elevation in blood pressure, renal vasoconstriction, and sodium retention. Several of such actions are similar to those of endothelin-1 (ET-1), which is the predominant isoform of the endothelin family in human vasculature. 3,4 Vasoactive properties of ET-1 are mediated by two receptor subtypes, ET A and ET B , both leading to vasoconstriction in vascular smooth cells, whereas activation of ET B in endothelial cells causes vasodilation as the result of release of prostacyclin and nitric oxide (NO). 3,4 In humans, however, the ET A receptor is the main mediator of ET-1 renal vasoconstriction. 5-8 ET-1, although it is the most potent endogenous vasoconstrictor, assumes a major hemodynamic role and contributes to the end-organ damage, mainly under experimental pathophysiological conditions. 3,4,9 -11 In most of these, interactions between Ang II and ET-1 may contribute largely to the observed changes. For instance, salt-sensitive hypertension, renal vasoconstriction, and cardiovascular and renal fibrotic damage, produced by chronic administration of exogenous Ang II, can be prevented by inhibition of endogenous ET-1, indicating that ET-1 mediates much of the vasoconstriction caused by chronic Ang II. 9 -11 Furthermore, ET-1 participates in the acute pressor effects of exogenous Ang II 12,13 and partly mediates the vasoconstriction from exogenous Ang II in different vascular beds, including kidney. 14,15 Interestingly, studies in rats have shown that such Ang II-ET-1 interaction may be sodium-dependent, because under elevated sodium intake, ET A blockade inhibited Ang II hypertension much more than under sodium restriction. 16 Ang II also stimulates both ET-1 synthesis and release, 3,4,17 whereas ET-1 enhances the pressor action of Ang II. 18 Finally, ET-1 and Ang II share the same intracellular signaling pathways. 3,17 Thus, ET-1 is generally considered as a powerful mediator of Ang II-dependent vasoconstriction and organ damage under experimental conditions. Conversely, little is known on the role of ET-1 and of its potential interactions with Ang II on systemic and renal hemodynamics in humans. In normal humans, systemic ET A blockade markedly blunts systemic and renal vasoconstr...

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“…9 Whereas these studies suggest a relation between Ang II and ET in the long-term regulation of arterial pressure, Riggleman et al have also shown that ET A receptor blockade prevents the renal vasoconstrictor actions of low doses of acutely administered Ang II and the natriuretic and diuretic actions of higher doses of Ang II in the rat. 10 More recently, Montanari et al had reported that an ET A selective antagonist inhibits the acute renal hemodynamic response to Ang II in humans. 11 This same group also provided evidence for ET A -dependent increases in renal vascular resistance in human subjects during AT 1 receptor blockade.…”

Section: Et-1 In Ang II Hypertensionmentioning

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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Endothelin Mediates Some of the Renal Actions of Acutely Administered Angiotensin II

Cited by 37 publications

References 34 publications

Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II

Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II

Endothelin-A Receptors Mediate Renal Hemodynamic Effects of Exogenous Angiotensin II in Humans

Endothelin, Angiotensin, and Oxidative Stress in Hypertension

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