Role of endothelin ET<sub>B</sub> receptor activation in angiotensin II-induced hypertension: effects of salt intake

Ballew, Jennifer R.; Fink, Gregory D.

doi:10.1152/ajpheart.2001.281.5.h2218

Cited by 24 publications

(33 citation statements)

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“…9 -12 Although the mechanisms of salt-sensitive hypertension have not been clearly identified, several studies point to a possible role of endothelin (ET). 7,[13][14][15][16][17] ET has been shown to interact with specific ET A and ET B receptors in tissues involved in the regulation of arterial pressure, particularly the kidney and the vasculature. 18 -24 Studies with specific ET A and ET B antagonists have suggested a possible role of ET as a mediator of angiotensin II-induced hypertension in rats, particularly during HS.…”

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confidence: 99%

“…18 -24 Studies with specific ET A and ET B antagonists have suggested a possible role of ET as a mediator of angiotensin II-induced hypertension in rats, particularly during HS. 14,15,17 However, whether ET directly affects the control mechanisms of arterial pressure is less clear. Recent studies have suggested a prominent role of ET in the control of renal plasma flow and renal sodium excretion and, thereby, the renal control mechanisms of arterial pressure.…”

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confidence: 99%

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Endothelin-Induced Increases in Ca ²⁺ Entry Mechanisms of Vascular Contraction Are Enhanced During High-Salt Diet

et al. 2003

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Abstract-High-salt diet is often associated with increases in arterial pressure, and a role for endothelin (ET)-1 in salt-sensitive hypertension has been suggested; however, the vascular mechanisms involved are unclear. We investigated whether ET increases the sensitivity of the mechanisms of vascular contraction to changes in dietary salt intake. Active stress and 45 Ca 2ϩ influx were measured in endothelium-denuded aortic strips of male Sprague-Dawley rats not treated or chronically infused intravenously with ET (5 pmol/kg per minute) and fed either normal-sodium diet (NS, 1%) or high-sodium diet (HS, 8%) for 9 days. Phenylephrine (Phe) caused increases in active stress that were similar in NS and HS, but were greater in NS/ET (maximum, 10.5Ϯ0.7) than in NS (maximum, 7.4Ϯ0.9) rats, and further enhanced in HS/ET (maximum, 14.4Ϯ1.1) compared with HS rats (maximum, 8.0Ϯ0.8ϫ10 4 N/m 2 ). Phe was more potent in causing contraction in NS/ET than in NS rats and in HS/ET than in HS rats. In Ca 2ϩ -free (2 mmol/L EGTA) Krebs, stimulation of intracellular Ca 2ϩ release by Phe (10 Ϫ5 mol/L) or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rats. In contrast, membrane depolarization by high-KCl solution, which stimulates Ca 2ϩ entry from the extracellular space, caused greater contraction in ET-infused rats, particularly those on HS diet. Phe (10 Ϫ5 mol/L) caused an increase in 45 Ca 2ϩ influx that was greater in NS/ET (27.9Ϯ1.7) than in NS (20.1Ϯ1.8) rats and further enhanced in HS/ET (35.2Ϯ1.8) compared with HS rats (21.8Ϯ1.9 mol/kg/min). The Phe-induced 45 Ca 2ϩ influx-stress relation was not different between NS and HS rats, but was enhanced in ET-infused rats particularly those on HS. The enhancement of the 45 Ca 2ϩ influx-active stress relation in ET-infused rats was not observed in vascular strips treated with the protein kinase C inhibitor GF109203X or calphostin C (10 Ϫ6 mol/L). Thus, low-dose infusion of ET, particularly during HS, is associated with increased vascular reactivity that involves Ca 2ϩ entry from the extracellular space, but not Ca 2ϩ release from the intracellular stores. The ET-induced enhancement of the Ca Key Words: arterial pressure Ⅲ endothelium Ⅲ vascular smooth muscle Ⅲ calcium Ⅲ contraction H igh-salt diet (HS) has been implicated in the pathogenesis of hypertension, particularly in salt-sensitive individuals, 1-4 and salt moderation is often recommended to protect against excessive increases in blood pressure. 1,2,5,6 Studies in salt-sensitive experimental animals such as the Dahl salt-sensitive rat have shown that HS is associated with significant increases in blood pressure. 7,8 Also, in saltsensitive rats, HS is associated with exaggerated vascular reactivity to vasoconstrictor stimuli, which may contribute, at least in part, to the increases in blood pressure. 9 -12 Although the mechanisms of salt-sensitive hypertension have not been clearly identified, several studies point to a possible role of endothelin (ET). 7,[13][14...

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Endothelin-Induced Increases in Ca ²⁺ Entry Mechanisms of Vascular Contraction Are Enhanced During High-Salt Diet

et al. 2003

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“…This is likely because the vascular and renal pressor effects of ET A receptors are counterbalanced by ET B receptor-mediated vasodilation and sodium excretion. In support of this theory, chronic ET B receptor blockade in rats is associated with increases in BP particularly during a high sodium diet (3,16,38).…”

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confidence: 79%

Dietary salt and hypertension: new molecular targets add more spice

Khalil

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…20 Briefly, systolic, diastolic, and mean APs (MAPs) and heart rate (HR) were recorded each morning between 8 and 11 AM. The transducers were connected to digital pressure monitors (Digi-Med blood pressure analyzer, Micro-Med) that provided input directly to a computerized digital pressure monitoring system.…”

Section: Cardiovascular Measurements: Standard Protocolmentioning

confidence: 99%

“…20 A separate group of rats received either S6c infusion (nϭ9) or saline vehicle infusion (nϭ8) using the standard protocol, and venous blood samples (1.2 mL) were drawn on control day 2, S6c infusion days 1 and 5, and on recovery day 2 for measurement of plasma ET-1 levels. The plasma was assayed using a commercial ELISA (ET-1 QuantiGlo chemiluminescent assay kit; R&D Systems), as described previously.…”

Section: Additional Measurementsmentioning

confidence: 99%

Chronic Activation of Endothelin B Receptors

Fink

Lau

et al. 2007

Hypertension

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Abstract-Endothelin (ET) exerts powerful pressor actions primarily through activation of the ET A receptor subtype. The ET B receptor (ET B R) subtype, on the other hand, is generally thought to initiate physiological actions that decrease arterial pressure. Such actions include clearing ET from the bloodstream, initiating endothelium-mediated vasodilation, and facilitating renal sodium and water excretion. The effect of long-term activation of the ET B R on arterial pressure, however, never has been directly tested. In this study we evaluated cardiovascular responses to chronic (5-day) activation of ET B R in male rats using continuous intravenous infusion of the selective agonist sarafotoxin 6c. Surprisingly, we found that sarafotoxin 6c caused a sustained increase in arterial pressure that rapidly reversed on termination of infusion. The hypertension was associated with increased renal excretion of sodium and water and decreased plasma volume. Alterations in daily sodium intake did not affect the magnitude of the hypertension. Hemodynamic studies revealed a decreased cardiac output and increased total peripheral resistance during sarafotoxin 6c infusion. Infusion of sarafotoxin 6c caused a small increase in plasma ET levels. Nevertheless, the hypertension was not affected by coadministration of a selective ET A receptor antagonist (atrasentan) but was completely prevented by treatment with a combined ET A receptor and ET B R antagonist (A186280). These experiments reveal for the first time that chronic activation of ET B R in rats causes sustained hypertension. (Hypertension. 2007;50:512-518.)Key Words: endothelin Ⅲ ET B receptor Ⅲ salt Ⅲ hemodynamics E ndothelins (ETs) have powerful effects on arterial blood pressure regulation and contribute to the genesis of human and experimental hypertension. 1 Most ET-mediated pressor actions result from stimulation of the ET A receptor (ET A R) found in vascular smooth muscle, kidney, heart, adrenal gland, and other tissues. 1 The influence of ET B receptor (ET B R) on arterial pressure (AP) regulation has been more controversial, but the bulk of evidence supports an antihypertensive function. Knockout of the ET B R gene causes salt-sensitive hypertension in rats 2 and mice, 3,4 as does chronic pharmacological blockade of ET B R in a variety of species. 5-8 One important antihypertensive mechanism associated with ET B R activation may be enhanced renal sodium and water excretion, because renal-collecting, duct-specific knockout of ET B R causes hypertension. 9 Other studies, however, do not support a critical role for renal ET B R in controlling AP. 2 ET B Rs on endothelial cells act as plasma ET clearance receptors, 10 and their absence or blockade produces increased plasma ET levels that can activate ET A R to cause hypertension. 6 In addition, ET B Rs located on endothelial cells promote vasodilation by releasing NO and prostanoids. Nevertheless, endothelial cell ET B Rs do not seem necessary for chronic AP regulation, because their selective deletion does not cause...

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Role of endothelin ET_B receptor activation in angiotensin II-induced hypertension: effects of salt intake

Cited by 24 publications

References 22 publications

Endothelin-Induced Increases in Ca ²⁺ Entry Mechanisms of Vascular Contraction Are Enhanced During High-Salt Diet

Endothelin-Induced Increases in Ca ²⁺ Entry Mechanisms of Vascular Contraction Are Enhanced During High-Salt Diet

Dietary salt and hypertension: new molecular targets add more spice

Chronic Activation of Endothelin B Receptors

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Role of endothelin ETB receptor activation in angiotensin II-induced hypertension: effects of salt intake

Cited by 24 publications

References 22 publications

Endothelin-Induced Increases in Ca 2+ Entry Mechanisms of Vascular Contraction Are Enhanced During High-Salt Diet

Endothelin-Induced Increases in Ca 2+ Entry Mechanisms of Vascular Contraction Are Enhanced During High-Salt Diet

Dietary salt and hypertension: new molecular targets add more spice

Chronic Activation of Endothelin B Receptors

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Role of endothelin ET_B receptor activation in angiotensin II-induced hypertension: effects of salt intake

Endothelin-Induced Increases in Ca ²⁺ Entry Mechanisms of Vascular Contraction Are Enhanced During High-Salt Diet

Endothelin-Induced Increases in Ca ²⁺ Entry Mechanisms of Vascular Contraction Are Enhanced During High-Salt Diet