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

Elijovich, Fernando; Laffer, Cheryl L.

doi:10.1038/sj.jhh.1001419

Cited by 16 publications

(8 citation statements)

References 98 publications

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“…All of these fragmentary observations make it difficult to offer a coherent explanation on the relationship that ANG II has with endothelin and OXST including salt metabolism. A recent review of Elijovich and Laffer (45) shows that most of the data in the literature strongly support the participation of endothelin in salt-sensitive hypertension. Furthermore, urinary endothelin excretion has also been shown to be increased by high sodium intake (141).…”

Section: Role Of Endothelin In Ang II Hypertensionmentioning

confidence: 99%

Role of oxidative stress in angiotensin-induced hypertension

Reckelhoff

Romero

2003

American Journal of Physiology-Regulatory, Integrative and Comp

167

133

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Reckelhoff, Jane F., and J. Carlos Romero. Role of oxidative stress in angiotensin-induced hypertension. Am J Physiol Regul Integr Comp Physiol 284: R893-R912, 2003; 10.1152/ajpregu.00491.2002.-Infusion of ANG II at a rate not sufficient to evoke an immediate vasoconstrictor response, produces a slow increase in blood pressure. Circulating levels of ANG II may be within ranges found in normotensive individuals, although inappropriately high with respect to sodium intake. When ANG II levels are dissociated from sodium levels, oxidative stress (OXST) occurs, which can increase blood pressure by several mechanisms. These include inadequate production or reduction of bioavailability of nitric oxide, alterations in metabolism of arachidonic acid, resulting in an increase in vasoconstrictors and decrease in vasodilators, and upregulation of endothelin. This cascade of events appears to be linked, because ANG II hypertension can be blocked by inhibition of any factor located distally, blockade of ANG II, OXST, or endothelin. Such characteristics are shared by other models of hypertension, such as essential hypertension, hypertension induced by reduction in renal mass, and renovascular hypertension. Thus these findings are clinically important because they reveal 1) uncoupling between ANG II and sodium, which can trigger pathological conditions; 2) the various OXST mechanisms that may be involved in hypertension; and 3) therapeutic interventions for hypertension developed with the knowledge of the cascade involving OXST.isoprostanes; endothelin; spontaneous hypertension; renovascular hypertension; sodium balance THREE DECADES AGO, the production of free radicals was thought to be the result of severe injuries or pathological insults such as those resulting from exposure to high-energy radiation or toxins such as carbon tetrachloride (127). However, in 1968, the discovery of superoxide dismutase (SOD) by McCord and Fridovich (96) strongly suggested that all aerobically metabolizing cells are capable of producing superoxide ions, which could play a role in normal metabolic processes. The concomitant discovery of the biology of nitric oxide (NO) strongly suggested that free radicals could constitute the basis of metabolic regulation (67,90,118). One of the first findings supporting such a notion was the demonstration that the inhibition of the synthesis of NO produced by the administration of an NO synthesis competitor, such as N -monomethyl-Larginine] or N G -nitro-L-arginine methyl ester (L-NAME), produced a marked vasoconstriction (13,136,173), sodium retention (82, 83), and thereby a sustained increase in mean arterial pressure (MAP) (13,82,83,136,173). The identification of a specific pathological situation in humans, where a decrease of NO may end up in an elevation of blood pressure was thought to be linked to endothelial dysfunction (105), such as those involved in aging, arteriosclerosis, etc., but the specific metabolic alterations involved in this process were poorly understood. However, the relationship betw...

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Section: Role Of Endothelin In Ang II Hypertensionmentioning

confidence: 99%

Role of oxidative stress in angiotensin-induced hypertension

Reckelhoff

Romero

2003

American Journal of Physiology-Regulatory, Integrative and Comp

167

133

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“…In hypertension, ETs play a greater role in salt-sensitive rodent models (eg, DOC-salt, aldosterone-induced, DahlSS, insulin-resistant, and 1K-1C Goldblatt models) and patients [69,70]. Their participation in exaggerated hypertrophic vascular remodeling and inflammation has been unequivocally demonstrated by the development of these abnormalities in mice with targeted endothelial overexpression of the human preproendothelin-1 gene, even though these animals do not develop hypertension [71].…”

Section: Endothelin Receptor Blockersmentioning

confidence: 99%

Inflammation and Therapy for Hypertension

Laffer

Elijovich

2010

Curr Hypertens Rep

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It is currently accepted that hypertension, atherosclerosis, and diabetes are disorders with subtle or overt activation of inflammatory mediators. Therefore, it has become increasingly important to ascertain whether current antihypertensive drug families have proinflammatory or anti-inflammatory actions that modify the outcomes of their hemodynamic effects on blood pressure. We review the current state of knowledge about the effects of the major classes of available antihypertensive agents on inflammation and speculate on the possible contribution of these effects to observations in clinical trials. We suggest that a strategy of drug development specifically addressing inflammation in hypertension may provide increased benefit in terms of target organ damage, and we describe some examples of these promising developments.

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“…Salt-depleted salt-sensitive hypertensives with blunted renin responses exhibit enhanced catecholamine-stimulated endothelin levels and may therefore respond better than unselected patients with essential hypertension to ERA [65]. Future clinical trials with ERA (perhaps more so, the ETA selective) will have a higher probability of demonstrating benefit if they focus on targeting salt-sensitive hypertensives preferentially.…”

Section: Salt-sensitive/low-renin Hypertensionmentioning

confidence: 99%

The future of endothelin-receptor antagonism as treatment for systemic hypertension

Vorobiof

Blaxall²,

Bisognano

2006

Current Science Inc

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Endothelin (ET) is an endogenous peptide secreted predominantly by endothelial cells that mediates its effects via vasoconstriction and hypertrophy of vascular smooth muscle. Because the role of ET has been described in multiple pathologic processes in cardiovascular disease, including hypertension, there has been a strong interest in the development of therapeutic agents that inhibit ET receptors. ET receptor antagonists have shown much promise in disease states such as pulmonary arterial hypertension, essential hypertension, and various forms of secondary hypertension. This review serves to summarize the current role of ET and ET receptor antagonists in both the pathophysiology and the treatment of hypertension.

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

Cited by 16 publications

References 98 publications

Role of oxidative stress in angiotensin-induced hypertension

Role of oxidative stress in angiotensin-induced hypertension

Inflammation and Therapy for Hypertension

The future of endothelin-receptor antagonism as treatment for systemic hypertension

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