Renal endothelin in heart failure and its relation to sodium excretion

Modesti, Pietro Amedeo; Cecioni, Ilaria; Costoli, Alessandro; Poggesi, Loredana; Galanti, Giorgio; Serneri, Gian Gastone Neri

doi:10.1067/mhj.2000.109917

Cited by 24 publications

(32 citation statements)

References 22 publications

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“…For example, the plasma ET-1 levels show dramatic increase in patients with heart failure (5.15 pg/mL) compared with control groups (0.75 pg/mL). Also, plasma levels of big ET-1 are greater in patients with heart failure (25.7 pg/mL) compared with control subjects (7.7 pg/mL) [42].…”

Section: Et Plasma/tissue Levels In Hypertensionmentioning

confidence: 99%

“…For example, the 24 hour urine levels of ET-1 show an increase in hypertensive patients with heart failure (17.0 ng/g UC) as compared to control subjects (1.7 ng/g UC) [42].…”

Section: Et Plasma/tissue Levels In Hypertensionmentioning

confidence: 99%

“…The 24-hour urinary ET excretion has been used as a predictor of ET levels, but the measurements show significant variability. For example, in normal adults, the 24-hour urinary excretion of ET could range between 1.7 pg/mL and 6.8 ng/mL [42,43]. Other forms of ET metabolism may involve its uptake by certain endothelial ET receptors that could function as "clearance receptors" [9].…”

Section: Et Metabolism/clearancementioning

confidence: 99%

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The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Hynynen

Khalil²

2006

PRC

107

105

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The discovery of endothelin two decades ago has now evolved into an intricate vascular endothelin (ET) system. Several ET isoforms, receptors, signaling pathways, agonists, antagonists, and clinical applications have been identified and documented in first-rate patents. The role of ET as one of the most potent endothelium-derived vasoconstricting factors is now complemented by a newly discovered role in vascular relaxation. ET synthesis is initiated by the transcription of ET genes in endothelial cells and the generation of the gene products preproET and big ET, which are further cleaved by specific ET converting enzymes into ET-1, -2, -3 and -4 isoforms. ET isoforms bind with different affinities to ET A and ET B2 receptors in vascular smooth muscle, and stimulate [Ca 2+ ] i , protein kinase C, mitogen-activated protein kinase and other signaling mechanisms of smooth muscle contraction, growth and proliferation. ET also binds to endothelial ET B1 receptors, which mediate the release of vasodilator substances such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor. Endothelial ET B1 receptors may also function in ET re-uptake and clearance. Although the effects of ET on vascular function and growth are well-recognized, the role of ET and its receptors in the regulation of blood pressure and in the pathogenesis of hypertension is not clearly established. Salt-dependent hypertension in experimental animals and some forms of moderate to severe hypertension in human may show elevated levels of plasma or vascular ET; however, other forms of hypertension show normal ET levels. The currently available ET receptor antagonists reduce blood pressure in some forms of experimental hypertension. Careful examination of recent patents may identify more effective and specific modulators of the vascular ET system for clinical use in human hypertension.

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Section: Et Plasma/tissue Levels In Hypertensionmentioning

confidence: 99%

“…For example, the 24 hour urine levels of ET-1 show an increase in hypertensive patients with heart failure (17.0 ng/g UC) as compared to control subjects (1.7 ng/g UC) [42].…”

Section: Et Plasma/tissue Levels In Hypertensionmentioning

confidence: 99%

Section: Et Metabolism/clearancementioning

confidence: 99%

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The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Hynynen

Khalil²

2006

PRC

107

105

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“…16,17 However, the relative temporal activation of myocardial and circulating ET-1 and the RAS systems during progression of CHF remains poorly defined. We therefore attempted to characterize the temporal activation of the ET-1 and RAS systems in myocardial tissue and plasma during transition to overt CHF, characterized by decreased sodium excretion, in a canine model of progressive LV dysfunction.…”

Section: See P 143mentioning

confidence: 99%

Endothelin A Receptor Antagonism in Experimental Congestive Heart Failure Results in Augmentation of the Renin-Angiotensin System and Sustained Sodium Retention

et al. 2004

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Background-While both the endothelin-1 (ET-1) and renin-angiotensin systems (RAS) are activated in congestive heart failure (CHF), the temporal sequence of this activation remains unclear. Understanding this pattern of neurohumoral activation may aid in understanding the significance of ET-1 in CHF and provide strategies for ET-1 antagonism. Although acute endothelin (ET) receptor antagonism improves systemic hemodynamics in CHF, clinical trials with chronic ET receptor antagonism report worsening CHF symptoms. Methods and Results-In a canine model of progressive left ventricular dysfunction, we demonstrated activation of myocardial and plasma ET-1 without activation of the RAS during transition to overt CHF, suggesting that ET-1 contributes to this transition. We next evaluated the effects of chronic oral ET-A receptor antagonism on neurohumoral function, renal hemodynamics, and sodium excretion in pacing-induced CHF. After 7 days of treatment (nϭ7) with ET-A receptor antagonism (with LU135252), sodium excretion did not improve in treated versus untreated CHF (nϭ6). Furthermore, both plasma renin activity and plasma ET-1 increased with ET-A receptor blockade. Conclusions-Activation

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“…10,11 In vivo, an increased renal ET-1 production has been found in pathophysiological and clinical conditions characterized by increased medulla osmolarity, such as dehydrated physical exercise, 12 low sodium diet, 2 and heart failure. 13 However, although cortical and medullary ET-1 systems participate differently in sodium and water handling, no studies exist comparing the activation of the ET-1 system in the 2 renal regions in the sodium-retentive states. Moreover, despite the fact that the use of ET-1 receptor antagonist has been proposed in heart failure, 14 -16 no information is available as to whether the increased local ET-1 synthesis is associated with a consensual increase in receptor synthesis or whether it may cause downregulation of its specific receptors.…”

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confidence: 99%

ET _B Receptor in Renal Medulla Is Enhanced by Local Sodium During Low Salt Intake

et al. 2002

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Abstract-Renal endothelin-1 participates in sodium and water handling, and its urinary excretion is increased in sodium-retentive states. We compared the cortical and medullary renal expression of prepro-endothelin-1, endothelinconverting enzyme-1, and endothelin type A and type B receptors in patients who underwent nephrectomy after normal (108 mmol/d NaCl; nϭ6) or low (20 mmol/d NaCl; nϭ6) sodium diet and investigated whether sodium exerts a direct role on endothelin receptor binding in vitro. With normal sodium diet prepro-endothelin-1 mRNA was 3-fold higher in renal medulla than in cortex (PϽ0.01), whereas endothelin-converting enzyme-1 mRNA was equally distributed. Endothelin-1 receptor density was 2-fold higher in renal medulla than in cortex (PϽ0.05). Type B was the main receptor subtype in both regions. In the renal cortex, low sodium diet caused a 194% increase in prepro-endothelin-1 mRNA (PϽ0.05), whereas endothelin-converting enzyme-1 type B and type A receptors remained unchanged. In contrast, in the renal medulla the increase in prepro-endothelin-1 mRNA (ϩ30%, PϽ0.05) was associated with a selective increase in type B receptor for both mRNA expression (ϩ37%, PϽ0.05) and binding density (ϩ55%, PϽ0.05). Increasing in vitro sodium concentrations between 154 and 308 mmol/L significantly enhanced type B receptor density (PϽ0.05) and affinity (PϽ0.05). In conclusion, during low sodium diet, renal prepro-endothelin-1 synthesis increases mainly in the renal cortex (where no changes in receptors occur), whereas type B receptor is selectively enhanced in the renal medulla.

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Renal endothelin in heart failure and its relation to sodium excretion

Cited by 24 publications

References 22 publications

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Endothelin A Receptor Antagonism in Experimental Congestive Heart Failure Results in Augmentation of the Renin-Angiotensin System and Sustained Sodium Retention

ET _B Receptor in Renal Medulla Is Enhanced by Local Sodium During Low Salt Intake

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Renal endothelin in heart failure and its relation to sodium excretion

Cited by 24 publications

References 22 publications

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Endothelin A Receptor Antagonism in Experimental Congestive Heart Failure Results in Augmentation of the Renin-Angiotensin System and Sustained Sodium Retention

ET B Receptor in Renal Medulla Is Enhanced by Local Sodium During Low Salt Intake

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ET _B Receptor in Renal Medulla Is Enhanced by Local Sodium During Low Salt Intake