Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ETA sub‐type

Davenport, Anthony P.; O’Reilly, Gillian; Kuc, Rhoda E.

doi:10.1111/j.1476-5381.1995.tb13322.x

Cited by 149 publications

(81 citation statements)

References 49 publications

(53 reference statements)

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“…The interpretation of this observation is complex for several reasons. First, the relative predominance of ET B receptor-mediated vasoconstriction or vasodilatation [12][13][14][15][16] will depend largely on the proportionate expression of these receptors in the vascular smooth muscle and endothelial cells. Selective cell-specific blockade of the ET B receptors would be valuable to dissect out these relative contributions but the techniques to address this issue do not currently exist.…”

Section: Discussionmentioning

confidence: 99%

“…In vascular smooth muscle cells, both receptors are expressed 11,12 and mediate vasoconstriction. [11][12][13][14] Only the ET B receptors are found on endothelial cells, where these cause vasodilatation through the release of endothelium-derived vasodilators, such as nitric oxide (NO). 15 ET-1-induced vasoconstriction is predominantly mediated by the ET A receptor, but ET B receptors may contribute under some circumstances.…”

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confidence: 99%

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Altered Peripheral Vascular Responses to Exogenous and Endogenous Endothelin–1 in Patients With Well–Compensated Cirrhosis

Helmy¹,

Jalan²,

Newby

et al. 2001

Hepatology

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Plasma endothelin concentrations are elevated in cirrhosis and correlate with disease severity. This study assessed forearm vascular responses to exogenous endothelin-1 (ET-1), and evaluated the contribution of endogenous ET-1 to the maintenance of basal peripheral vascular tone in patients with well-compensated cirrhosis (n ‫؍‬ 11) and matched healthy controls (n ‫؍‬ 8). Bilateral forearm blood flow (FBF) was measured at baseline and following unilateral, subsystemic, intrabrachial artery infusions of ET-1 (2 and 6 pmol/min); BQ-123, a selective ET A receptor antagonist (3 and 10 nmol/min); and BQ-788, a selective ET B receptor antagonist (0.3 and 1 nmol/min) using venous occlusion plethysmography. Baseline systemic hemodynamics and plasma ET-1 and big ET-1 concentrations were measured using electrical bioimpedance and radioimmunoassay, respectively. Patients and controls had similar baseline FBF, systemic hemodynamics, and plasma ET-1 and big ET-1 concentrations. In both groups, ET-1 and BQ-788 caused significant vasoconstriction (P < .001) and BQ-123 caused significant vasodilatation (P < .001). Compared with controls, cirrhotic patients had attenuated ET-1 responses (P < A hyperdynamic circulation characterized by low arterial pressure, high cardiac output, and low systemic vascular resistance is a feature of patients with advanced cirrhosis and portal hypertension. [1][2][3] This hyperdynamic circulation worsens with disease progression [4][5][6] and is accompanied by a reduced reactivity to vasopressor systems including the reninangiotensin and sympathetic nervous systems. These hemodynamic changes play a crucial role in the pathogenesis of portal hypertension and its complications, including variceal hemorrhage, ascites, and the hepatorenal syndrome. 7,8 Endothelin-1 (ET-1) is the most potent vasoconstrictor known, belonging to a 21-amino acid peptide family with a range of biological effects. 9-11 ET-1 was originally identified in the culture medium of porcine aortic endothelial cells 9,10 and is derived from a larger pre-pro-endothelin-1 (212 amino acids), which is cleaved by endopeptidases to produce big ET-1 (38 amino acids), which is then converted to ET-1 by specific endothelin-converting enzymes. [9][10] Molecular studies have, so far, identified 2 endothelin receptor subtypes in mammalian species: endothelin-A (ET A ) and endothelin-B (ET B ). In vascular smooth muscle cells, both receptors are expressed 11,12 and mediate vasoconstriction. [11][12][13][14] Only the ET B receptors are found on endothelial cells, where these cause vasodilatation through the release of endothelium-derived vasodilators, such as nitric oxide (NO). 15 ET-1-induced vasoconstriction is predominantly mediated by the ET A receptor, but ET B receptors may contribute under some circumstances. 16 Since 1991, many studies have reported increased plasma concentrations of ET-1 in patients with cirrhosis. [17][18][19][20][21][22][23][24][25][26] The mechanisms underlying the elevated ET-1 concentrations are unclear and do not appe...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Altered Peripheral Vascular Responses to Exogenous and Endogenous Endothelin–1 in Patients With Well–Compensated Cirrhosis

Helmy¹,

Jalan²,

Newby

et al. 2001

Hepatology

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“…The distribution of both ETA and ETB receptors is widely localized throughout the body (6,7,8,16). Within the vasculature, the predominant effect of ETA stimulation is vasoconstriction.…”

Section: Introductionmentioning

confidence: 99%

PD‐156707: A Selective Endothelin‐A Receptor Antagonist

Uprichard¹,

Metz²,

Hallak³

et al. 1998

Cardiovascular Drug Reviews

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“…Activation by ET-1 of the ETB receptor located on endothelial cells results in a release of nitric oxide (NO) and prostacyclin to cause vasodilatation (De Nucci et al, 1988;Thiemermann et al, 1989). ETB receptors also exist on vascular smooth muscle cells of certain blood vessels of a variety of species including rats, pigs, dogs (Ihara et al, 1991;Bigaud & Pelton, 1992;Teerlink et al, 1994) and man (Davenport et al, 1995), where they mediate vasoconstriction.…”

Section: Introductionmentioning

confidence: 99%

Effect of selective blockade of endothelin ET_B receptors on the liver dysfunction and injury caused by endotoxaemia in the rat

Ruetten

Thiemermann

1996

British J Pharmacology

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1 We investigated the effects of the selective endothelin (ET)A receptor antagonist BQ-485 and the selective ETB receptor antagonist BQ-788 on circulatory failure, multiple organ dysfunction syndrome (MODS) and the alterations in acid base balance caused by endotoxaemia in the anaesthetized rat. 2 Male Wistar rats were anaesthetized (thiopentone sodium; 120 mg kg-', i.p.) and received a continuous infusion of vehicle (saline, 0.6 ml kg-'h-', i.v.), i.v.) or i.v.). Fifteen min later, animals received a bolus injection of either saline (0.9% NaCl, 1 ml kg-', i.v.) or E. coli lipopolysaccharide (LPS, 10 mg kg-', i.v.). 3 Injection of LPS resulted in a fall in blood pressure from 115 + 4 mmHg (time 0) to 82 + 4 mmHg at 360 min (n = 15) as well as a hyporeactivity to the pressor responses to noradrenaline (NA, 1 jug kg-', i.v.). Infusion of BQ-788 attenuated the delayed hypotension (at 360 min: 100 + 4 mmHg, n = 7; P < 0.05) and significantly enhanced the pressor responses elicited by NA (at 60 to 240 min). In contrast, treatment of LPS-rats with BQ-485 augmented the hypotension (at 360 min), but did not affect the vascular hyporeactivity elicited by endotoxaemia. 4 Endotoxaemia for 360 min resulted in rises in the serum levels of urea and creatinine (indicators of renal failure), glutamate-oxalate-transferase (GOT) and glutamate-pyruvate-transferase (GPT) (indicators of hepatocellular injury), and bilirubin and 'y-glutamyl transferase (yGT) (indicators of liver failure) as well as nitrite (indicator of the induction of nitric oxide synthase; iNOS). Treatment of LPS-rats with BQ-788, but not with BQ-485, attenuated the degree of liver injury and failure, while neither BQ-788 nor BQ-485 affected the acute renal failure or the induction of iNOS caused by endotoxin. 5 Endotoxaemia also caused (within 15 min) an acute metabolic acidosis (falls in pH, HCO3-and base excess) which was compensated by hyperventilation (fall in Paco2). Treatment of LPS-rats with BQ-788 or BQ-485 did not affect the metabolic acidosis caused by LPS.6 Thus, the selective ETB receptor antagonist BQ-788 attenuated (i) the delayed hypotension, (ii) the vascular hyporeactivity to NA as well as (iii) the degree of hepatocellular injury and dysfunction caused by endotoxin in the anaesthetized rat. In contrast, the selective ETA receptor antagonist did neither attenuate the circulatory failure nor the liver or renal dysfunction associated with endotoxaemia. We propose that the prevention of the hepatocellular dysfunction and injury caused BQ-788 in endotoxaemia is due to an improvement in oxygen delivery to the liver secondary to (i) inhibition of pre-sinusoidal constriction, (ii) inhibition of sinusoidal constriction, and (iii) improvement in perfusion pressure.

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Endothelin ET_A and ET_B mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ET_A sub‐type

Cited by 149 publications

References 49 publications

Altered Peripheral Vascular Responses to Exogenous and Endogenous Endothelin–1 in Patients With Well–Compensated Cirrhosis

Altered Peripheral Vascular Responses to Exogenous and Endogenous Endothelin–1 in Patients With Well–Compensated Cirrhosis

PD‐156707: A Selective Endothelin‐A Receptor Antagonist

Effect of selective blockade of endothelin ET_B receptors on the liver dysfunction and injury caused by endotoxaemia in the rat

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Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ETA sub‐type

Cited by 149 publications

References 49 publications

Altered Peripheral Vascular Responses to Exogenous and Endogenous Endothelin–1 in Patients With Well–Compensated Cirrhosis

Altered Peripheral Vascular Responses to Exogenous and Endogenous Endothelin–1 in Patients With Well–Compensated Cirrhosis

PD‐156707: A Selective Endothelin‐A Receptor Antagonist

Effect of selective blockade of endothelin ETB receptors on the liver dysfunction and injury caused by endotoxaemia in the rat

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Product

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Endothelin ET_A and ET_B mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ET_A sub‐type

Effect of selective blockade of endothelin ET_B receptors on the liver dysfunction and injury caused by endotoxaemia in the rat