Endothelin ETA and ETB Receptors Mediate Vascular Smooth-Muscle Contraction

White, David G.; Cannon, Toby R.; Garratt, H; Mundin, Jason W.; Sumner, Michael; Watts, Ian S.

doi:10.1097/00005344-199322008-00039

Cited by 46 publications

(28 citation statements)

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“…In the present work, the antagonist of endothelin ET A receptors, BQ-123, significantly inhibited the contractile response of the carotid artery to endothelin-1, both in control (increased the EC 50 value, without affecting the E max ) and diabetic (increased the EC 50 value and inhibited the E max ) rabbits. These results confirm that the contraction of the rabbit carotid artery in response to endothelin-1 is mediated by endothelin ET A receptors, as has been previously reported in the rabbit carotid artery (White et al, 1993;Calo et al, 1996). BQ-123 inhibited the maximal contraction elicited by endothelin-1 in carotid arteries from diabetic rabbits but not in control rabbits, suggesting a greater participation of endothelin ET A receptors in diabetes, which could partially contribute to the hyperreactivity of the rabbit carotid artery to endothelin-1 in diabetes.…”

Section: Discussionsupporting

confidence: 92%

“…There is controversy about the presence of endothelin ET B receptors in the rabbit carotid artery. Several studies have failed to find endothelin ET B receptors in this artery (White et al, 1993;Lodge et al, 1995;Calo et al, 1996). Because endothelin ET B activation mediates opposite effects depending of the endothelial or muscular location of the receptor, the sum of these effects could have masked the effect of the activation of each of them individually.…”

Section: Discussionmentioning

confidence: 96%

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Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1

Lloréns

Miranda

Alabadí

et al. 2004

European Journal of Pharmacology

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The influence of diabetes on regulatory mechanisms and specific receptors implicated in the contractile response of isolated rabbit carotid arteries to endothelin-1 was examined. Endothelin-1 induced a concentration-dependent contraction that was greater in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal or N G -nitro-L-arginine enhanced contractions in response to endothelin-1 only in control arteries, without modifying the endothelin-1 response in diabetic arteries. Indomethacin, furegrelate (thromboxane A 2 inhibitor), or cyclo-(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123; endothelin ET A receptor antagonist) inhibited the contractions in response to endothelin-1, the inhibition being greater in diabetic arteries than in control arteries. 2,6-Dimethylpiperidinecarbonyl-g-methyl-Leu-N in -(methoxycarbonyl)-D-Trp-D-Nle (BQ-788; endothelin ET B receptor antagonist) enhanced the contraction elicited by endothelin-1 in control arteries and displaced to the right the contractile curve for endothelin-1 in diabetic arteries. In summary, diabetes induces hyperreactivity of the rabbit carotid artery to endothelin-1 by a mechanism that at least includes: (1) enhanced activity of muscular endothelin ET A receptors; (2) impairment of endothelin ET B receptor-mediated nitric oxide (NO) release; and (3) enhancement of the production of thromboxane A 2 .

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 96%

Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1

Lloréns

Miranda

Alabadí

et al. 2004

European Journal of Pharmacology

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“…However, in isolated myocytes mRNA encoding both sub-types was found and BQ123 inhibited binding of iodinated ET-1 biphasically, confirming that both receptor sub-types were present in these cells , myometrium and kidney cortex and medulla . Intriguingly, Bax et al (1993) (Maguire & Davenport, 1995 Davis et al, 1991;Clozel et al, 1992;Sumner et al, 1992;Cristol et al, 1993;Gardiner et al, 1994;Pollock & Opgenorth, 1993;Wellings et al, 1994;White et al, 1994a) whereas constriction appears to be mediated only by ETA receptors in rat aorta (Sumner et al, 1992) or rabbit renal artery (Telemarque et al, 1993) but both sub-types are activated in porcine coronary artery (Ihara et al, 1992).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

“…[1110][1111][1112][1113][1114][1115][1116] In animals, ET-l can elicit constriction through both ETA and ETB receptors although the pattern is complex: the subtype ratio varies in different vascular beds in the same species and in the same vascular bed in different species . For example, constriction appears to be mediated only by ETA receptors in rat aorta (Sumner et al, 1992) but by ETB receptors in rabbit pulmonary artery (White et al, 1994a). In porcine coronary artery, the ETA selective antagonist, BQ123 does not block all of the ET-1-induced contraction, indicating activation of both sub-types (Ihara et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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

Davenport

O’Reilly

Kuc

1995

British J Pharmacology

149

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1 We measured the ratio of ETA and ETB sub-types in the media (containing mainly smooth muscle) of human cardiac arteries (aorta, pulmonary and coronary), internal mammary 4 A single band corresponding to the expected position for mRNA encoding the ETA receptor (299 base pairs) was found in the media in each of the five vessels (n = 3 individuals) using reversetranscriptase polymerase chain reaction assays. A single band corresponding to the ETB sub-type (428 base pairs) was also always detected. 5 35S-labelled antisense probes to ETA and ETB hybridised to the media of epicardial coronary arteries as well as intramyocardial vessels, confirming the presence of mRNA encoding both sub-types in the vascular smooth muscle of the vessel wall. 6 Although mRNA for both receptors was detected, competition binding using BQ123 demonstrated that the majority (at least 85%) of ET receptors present in smooth muscle are the ETA sub-type. These results provide further support for the hypothesis that the ETA sub-type is the receptor that must be blocked in humans to produce a beneficial vasodilatation in pathophysiological conditions where there is an increase in peptide concentration or receptor density.

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“…There is evidence that both support and negate the involvement of the ET B receptor in mediating contraction in arteries. For example, the ET B receptor agonists sarafotoxin 6c (S6c) and IRL1620 do not cause arterial contraction directly in many arterial beds and isolated arteries (e.g., White et al, 1993;Caló et al, 1996;Thakali et al, 2004). However, as supported through antagonism studies, ET B receptors mediate contraction in arteries from special circulations, including the coro-nary artery (Bax et al, 1994;Sudjarwo et al, 1995), pulmonary artery (Teerlink et al, 1994;Montagnani et al, 2000), and skin .…”

mentioning

confidence: 99%

Endothelin ET_BReceptors in Arteries and Veins: Multiple Actions in the Vein

Tykocki

Gariepy

Watts

2009

J Pharmacol Exp Ther

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Endothelin receptors (ET A and ET B ) mediate responses to ET-1. ET B receptor function seems to differ between a similarly sized arterial and venous pair, the rat vena cava (RVC) and rat thoracic aorta (RA). ET B receptors mediate RVC contraction directly, but it is unclear whether ET B receptors mediate contraction in RA. Because of these apparent differences in ET B receptor-mediated vascular contraction, we hypothesize that relaxant ET B -receptor mechanisms in RVC would be different from those in RA. RA and RVC rings were isolated from rats for measurement of isometric contraction. When contracted with prostaglandin F-2␣ (PGF-2␣) (20 M), the ET B receptor agonist sarafotoxin-6c (S6c) (100 nM) significantly relaxed RA and RVC. N -Nitro-L-arginine (LNNA) (100 M) or endothelial denudation abolished relaxation to S6c in RA. By contrast, S6c-induced relaxation of RVC was attenuated but not abolished by LNNA and endothelial denudation. RVC (PGF-2␣-contracted) relaxed to low concentrations of ET-1, whereas under the same conditions RA responded with contraction. ET-1-induced relaxation in RA was observed only with ET A receptor blockade. Vessels from dopamine-␤-hydroxylase-ET B transgenic rats, which lack functional ET B receptors in the vasculature, were also used. RVC (PGF-2␣-contracted) from these rats did not relax to ET-1. Thus, although both RA and RVC possess endothelial relaxant ET B receptors, RA and RVC differ in that relaxant ET B receptors may also be present in smooth muscle of RVC. Moreover, the mechanisms of endothelial cell ET B receptor-mediated relaxation in RA and RVC are not the same.Endothelin-1 (ET-1) is a 21-amino acid peptide that acts as a potent endogenous vasoconstrictor (Schiffrin, 1999). Although also made by other cell types, the dominant producers of ET-1 in the vasculature are endothelial cells. ET-1 has been implicated in the pathology of pulmonary arterial hypertension as well as systemic hypertension models, including deoxycorticosterone acetate-salt hypertension (Böhm and Pernow, 2007). ET-1 binds to and activates two G proteincoupled receptor subtypes: the ET A and ET B receptor (Davenport, 2002). In both arteries and veins, ET A receptor stimulation causes contraction (Zhang et al., 1999). In contrast, the role of ET B receptors is much less clear and differs between vessel types.Several reports characterize the ET B receptor as a "clearance receptor," the primary function of which is to sequester and remove circulating ET-1 from the blood (Fukuroda et al., 1994). In this capacity, ET B receptors decrease the amount of ET-1 available to interact with ET A receptors and thus decrease vascular contraction because of ET A receptor stimulation. Researchers have since discovered that ET B receptor stimulation can directly modulate vascular tone in arteries and veins, albeit with different functions. In arteries, functional ET B receptors exist in endothelial cells, in which receptor stimulation causes relaxation by increasing endothelial nitric oxide production (Tsukahara e...

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Endothelin ETA and ETB Receptors Mediate Vascular Smooth-Muscle Contraction

Cited by 46 publications

References 1 publication

Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1

Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1

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

Endothelin ET_BReceptors in Arteries and Veins: Multiple Actions in the Vein

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Endothelin ETA and ETB Receptors Mediate Vascular Smooth-Muscle Contraction

Cited by 46 publications

References 1 publication

Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1

Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1

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

Endothelin ETBReceptors in Arteries and Veins: Multiple Actions in the Vein

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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

Endothelin ET_BReceptors in Arteries and Veins: Multiple Actions in the Vein