Elevated Immunoreactive Endothelin Levels in Patients With Pheochromocytoma

Oishi, Seiichi; Sato, Masato; Satô, Tatsuo

doi:10.1093/ajh/7.8.717

Cited by 26 publications

(21 citation statements)

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“…Significantly higher levels of ET-1 were seen in those with phaeochromocytoma compared with the 2 other groups, and, among these, the presence of hypertension was associated with the highest plasma ET-1 concentrations. These findings supported a role for ET-1 in the development of clinical hypertension, 44 although many solid cancers generate ET-1. In agreement with preclinical data, which suggested that the ET system was primarily activated in the more severe rodent models of BP elevation (such as deoxycorticosterone acetate-salt, Dahl salt-sensitive, and stroke-prone spontaneously hypertensive rats), the increased prepro-ET-1 message is found in the endothelium of small arteries of patients with moderate-tosevere hypertension.…”

Section: Essential Hypertensionsupporting

confidence: 53%

Role of Endothelin-1 in Clinical Hypertension

et al. 2008

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H ypertension is the most common risk factor worldwide for cardiovascular morbidity and mortality. 1,2 Currently it is estimated that a quarter of the world's adult population is hypertensive, and this number is projected to increase to Ϸ30% by 2025. 1 Although, there exist a number of drug therapies for hypertension, blood pressure (BP) control to target is still only achieved in Ϸ30% of patients. 3 Over the last 20 years, novel licensed therapies have primarily focused on the renin-angiotensin-aldosterone system. Endothelin (ET) receptor antagonism represents an innovative, but as yet only partially explored, alternative approach in the management of hypertension.A review in Hypertension 10 years ago outlined the potential role that ET-1 may play in the development of hypertension, 4 as proposed by Yanagisawa et al in their original Nature article in 1988. 5 This largely focused on preclinical data because, at that time, there was only 1 published study of ET receptor antagonism in patients with essential hypertension. 6 There were also few data that focused on the relative benefits of selective or mixed ET blockade. Finally, the lack of longer-term data on safety and tolerability for these drugs made their place in the antihypertensive armamentarium unclear. In this review we aim to answer many of these questions and outline some of the key findings in this field from the last decade. Biology of the ET SystemThe ET family consists of three 21-amino acid peptides (ET-1, ET-2, and ET-3) with powerful vasoconstrictor and pressor properties. 7 Of the 3 peptides, ET-1 is the major vascular isoform and of most importance in the cardiovascular system. 8 The gene product is the 212-amino acid prepro-ET-1. This is cleaved to big ET-1, after which an ETconverting enzyme (ECE) catalyzes the generation of the biologically active ET-1 and a C-terminal fragment.ET-1 acts by binding to 2 distinct receptors, the ET A and the ET B receptors (ET A R and ET B R). 9,10 ET receptors are expressed by a wide variety of cells and tissues. Within the vasculature, ET A R and ET B R, located on vascular smooth muscle cells, mediate the vasoconstrictor effects of ET B Rs are also found on vascular endothelial cells, where their activation results in vasodilation mediated mainly by NO. 12,13 In addition, ET B Rs have a major role in the clearance of circulating ET-1. The plasma half-life of ET-1 in health is Ϸ1 minute, 14 with removal through receptor-and nonreceptormediated mechanisms. ET-1 binds to ET B R, with subsequent ligand-receptor complex internalization and intracellular degradation accounting for the majority of clearance, particularly in the pulmonary circulation, 15 although the splanchnic and renal circulations also contribute. 16 Therefore, a reduction in ET B R number, or ET B R blockade, may reduce ET-1 clearance, increasing plasma concentrations without altering production. For this reason and, importantly, because most ET-1 is released albuminally, plasma concentrations of ET-1 do not accurately reflect ET-1 productio...

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Section: Essential Hypertensionsupporting

confidence: 53%

Role of Endothelin-1 in Clinical Hypertension

et al. 2008

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“…This raises the suspicion about the role of ET in the pathogenesis of primary hyperaldosteronism (16). In pheochromocytoma, ET stimulates catecholamine release by the adrenal medulla and is secreted excessively together with the catecholamines (11). Available data show that it is hardly likely that the pituitary is the source of elevated ET-1 secretion in the ACTH-dependent Cushing's syndrome caused by corticotropinoma, since it was found that this peptide was expressed by both ACTH-secreting bronchial carcinoid and corticotropinomas (18,19).…”

Section: Discussionmentioning

confidence: 99%

Elevated plasma endothelin as an additional cardiovascular risk factor in patients with Cushing's syndrome

Кirilov¹,

Tomova²,

Dakovska³

et al. 2003

European Journal of Endocrinology

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Background: Recently the pathophysiological role of endothelin (ET) has been presumed in a number of adrenal disorders such as primary hyperaldosteronism, pheochromocytoma and adrenocortical insufficiency. Aim: The aim of the present study was to evaluate circulating ET-1 levels in patients with endogenous Cushing's syndrome. Methods and results: Plasma ET-1 levels were determined by highly sensitive RIA. Thirteen untreated subjects with Cushing's syndrome were studied: eight women and five men of mean age 44.2^9.5 years (S.D.). In ten of them, Cushing's disease had been diagnosed and three had adrenal adenomas. ET-1 was 3-fold higher in the patient group than in age-matched healthy controls (n ¼ 13): 1.59^0.78 vs 0.46^0.20 pmol/l respectively, P , 0.001. In adrenal adenoma patients, ET-1 was not significantly higher than in the Cushing's disease subjects (1.84^0.67 vs 1.51^0.83 pmol/l respectively, P . 0.05). In three patients who died of severe cardiovascular complications, plasma ET-1 was significantly higher than in the remaining patients (2.34^0.35 pmol/l, P , 0.05). A positive correlation was found between the total cholesterol (6.94^1.75 mmol/l) and ET-1 levels in the patients with Cushing's syndrome: r ¼ þ0.73, P , 0.02. No correlation was observed, however, between the levels of ET-1 and blood pressure (183^37/106^18 mmHg), plasma cortisol levels (455.2^74.5 nmol/l) or urinary cortisol excretion (1463^726 nmol/24 h). The successful treatment and correction of hypercortisolism in seven patients led to insignificant reduction in plasma ET from 1.34^0.69 to 0.73^0.53 pmol/l, P . 0.05. Conclusion: Our results clearly demonstrate that the ET system is activated in Cushing's syndrome. Elevated plasma ET-1 levels probably play a role in the pathogenesis of accelerated and early atherosclerosis development in this disorder.

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“…In contrast to patients with primary hvperaldosteronism. endothelin-1 is elevated in pheochromocytoma [83], Moreover, a patient with endothelinsecreting hemangioendothelioma exhibited hypertension which normalized after the tumor had been resected [84], Since at least two thirds are released abluminally towards the vascular smooth muscle cells, endothelin-1 plasma levels do not reflect local levels of the peptide [85]. Nev ertheless.…”

Section: Genetic Hypertensionmentioning

confidence: 99%

The Endothelium in Coronary Artery Disease

Ruschitzka

Noll

Lüscher³

1997

Cardiology

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An increasing body of evidence indicates that the endothelium is crucially involved in the regulation of coronary blood flow and cardiac function. Injury to the endothelium precipitates atherosclerosis by leading to smooth-muscle-cell migration and proliferation, induction of expression of growth factors and impairment in the plasmatic coagulation and endogenous fibrinolysis system. Strategically located between the circulating blood and the vascular smooth muscle, endothelial cells release numerous vasoactive substances regulating the function of vascular smooth muscle and trafficking blood cells. Important endothelium-derived vasodilators are prostacyclin, bradykinin, nitric oxide and, independent of the former, endothelium-derived hyperpolarizing factor. In particular, nitric oxide inhibits cellular growth and migration. In concert with prostacyclin, nitric oxide exerts potent antiatherogenic and thrombore-sistant properties by preventing platelet aggregation and cell adhesion. These effects are counterbalanced by endothelial vasoconstrictors, such as angioten-sin II and endothelin-1 both of which exert prothrombotic and growth-promoting properties. Modern therapeutic strategies in coronary artery disease focus on preserving or restoring endothelial integrity. Whereas nitrates partly substitute deficient endogenous nitric oxide, calcium antagonists counteract angiotensin II and endothelin-1 at the level of vascular smooth muscle by reducing Ca²⁺ inflow and facilitating the vasodilator effects of nitric oxide. Beyond inhibiting the renin-angiotensin system, angiotensin-converting enzyme inhibitors diminish the inactivation of bradykinin, thus leading to an augmentation of nitric oxide release. Furthermore, newly developed specific endothelin antagonists will provide us with greater insight into the beneficial effects of restoring endothelial dysfunction in cardiovascular disease. Thus, drugs can directly affect endothelial function, prevent the action of endothelial mediators, substitute for deficient endothelial factors or indirectly exert protective effects by interfering with cardiovascular risk factors.

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Elevated Immunoreactive Endothelin Levels in Patients With Pheochromocytoma

Cited by 26 publications

References 0 publications

Role of Endothelin-1 in Clinical Hypertension

Role of Endothelin-1 in Clinical Hypertension

Elevated plasma endothelin as an additional cardiovascular risk factor in patients with Cushing's syndrome

The Endothelium in Coronary Artery Disease

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