Endothelin receptor expression and pharmacology in human saphenous vein graft

Maguire, Janet J.; Davenport, Anthony P.

doi:10.1038/sj.bjp.0702326

Cited by 27 publications

(16 citation statements)

References 50 publications

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“…4B). These results altogether indicate that ET A , but not ET B , is the predominant vasoconstrictor ET receptor in the mouse abdominal aorta, which concurs with reports on several rat as well as human vessels (5,8,12,21,22,25).…”

Section: Discussionsupporting

confidence: 93%

“…As demonstrated by the concentration-response curve obtained with the presence of NOS inhibitor L-NAME, ET-1-induced contractile response in the mouse abdominal aorta is as potent as those in human vessels, such as saphenous vein graft (12). Thus it is clear that ET receptors play a significant role in mediating the vasoconstriction in mice.…”

Section: Discussionmentioning

confidence: 95%

“…In contrast, ET B receptors exist both in the smooth muscle and in the endothelial cells (13,14). While ET B receptors present in the smooth muscle mediate vasoconstriction (13,14,24), those in the endothelial cell cause vasodilation via the release of endothelium-dependent relaxing factors, such as nitric oxide (NO) (12,17,23). However, it has been recently found that part of the depressor effect of ET B receptor may be related to the clearance of ET-1 in the plasma (3,5).…”

mentioning

confidence: 92%

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Endothelin-1-induced responses in isolated mouse vessels: the expression and function of receptor types

Zhou¹,

Dirksen²,

Zweíer³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Mice have been increasingly used as models for investigating cardiovascular diseases. However, the responsiveness of mouse vasculature to endothelin (ET)-1 has not been clearly established. The goal of this study was to determine the role of ET receptors (ET(A) and ET(B)) in mouse vessels using isometric force measurements. Results showed that in the abdominal aorta ET-1 induced a concentration-dependent contraction (EC(50): 1.4 nM) with maximum reaching 89.5 +/- 4.9% (10 nM) of that induced by 60 mM K(+) [with nitric oxide synthase (NOS) inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME)]. However, in the thoracic aorta or the carotid artery, ET-1 was poorly effective. RT-PCR revealed that in the endothelium-denuded abdominal aorta, the PCR product for ET(B) receptors was very low compared with ET(A). Similarly in tissues treated with l-NAME, the ET(B) receptor-specific agonist sarafotoxin 6c (S6c; 100 nM) induced only a minimal contraction (<5%). Meanwhile, the ET(A) antagonist BQ-123 (1 microM) completely inhibited the maximum ET-1 (10 nM) contractile response. Furthermore, we found that in the abdominal aorta that had not been treated with l-NAME, ET-1-induced contraction significantly decreased. However, in such specimens, S6c was unable to induce any relaxation on phenylephrine-induced contraction. These results indicate that the role of ET receptors differs considerably among mouse vessels. In the abdominal aorta, ET(A) receptor mediates a potent vasoconstrictor response, whereas ET(B) has, if any, only a minimal functional presence. Also, our data suggest that ET-1 might involve a NOS-dependent vasodilation in the abdominal aorta, which remains to be further defined.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 92%

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Endothelin-1-induced responses in isolated mouse vessels: the expression and function of receptor types

Zhou¹,

Dirksen²,

Zweíer³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…32 In a related setting of pressure-induced gene expression (ie, angioplasty), on the other hand, evidence has been provided that points to an important role for the ET B -R or a non-ET A -R/non-ET B -R in the rabbit 33 and rat carotid artery 34 -36 in restenosis. Therefore, further studies in an appropriate animal model (ie, jugular vein-carotid artery interposition graft) are required to substantiate the hypothesis of an ET-1-induced ET B -Rmediated proliferative response in aortocoronary venous bypass grafts.…”

Section: Discussionmentioning

confidence: 99%

Pressure-Induced Upregulation of Preproendothelin-1 and Endothelin B Receptor Expression in Rabbit Jugular Vein In Situ

Lauth

Berger

Cattaruzza

et al. 2000

ATVB

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Abstract-Upregulation of endothelin-1 (ET-1) synthesis in venous bypass grafts in response to arterial levels of blood pressure may play a major role in graft failure. To investigate this hypothesis, isolated segments of the rabbit jugular vein were perfused at physiological (0 to 5 mm Hg) and nonphysiological (20 mm Hg) levels of intraluminal pressure.As judged by reverse transcription-polymerase chain reaction analysis (mRNA level), neither endothelin-converting enzyme nor endothelin A receptor expression appeared to be pressure sensitive. In contrast, there was a profound and time-dependent increase in endothelial prepro-ET-1 mRNA and intravascular ET-1 abundance (by ELISA) as well as in smooth muscle endothelin B receptor mRNA and functional protein (by superfusion bioassay) on raising the perfusion pressure from 5 to 20 mm Hg, but not from 0 to 5 mm Hg, for up to 12 hours. Video microscopy analysis revealed that the segments were distended by 75% at 5 mm

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“…In healthy and grafted saphenous vein, vasoconstriction is mediated predominantly via the ET A receptor, with no increased contribution from the smooth muscle ET B receptors in failed grafts [4,6]. ET-1 stimulated DNA synthesis in cultured human saphenous vein smooth muscle [7,8] and induced neointimal thickening in human saphenous vein in organ culture [8].…”

Section: Introductionmentioning

confidence: 99%

ETA receptor antagonists inhibit intimal smooth muscle cell proliferation in human vessels

Maguire

Davenport

2002

Clinical Science

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We have determined the ability of the endothelin (ET)(A) receptor antagonist, PD156707 (CI 1020), to inhibit intimal proliferation in human saphenous veins maintained in organ culture. After 28 days in culture, veins exposed to 1 microM PD156707 exhibited a significant reduction in intima to intima-plus-media ratio (I:I+M ratio) (0.14+/-0.02, n=15) and an increase in lumen area (3.1+/-0.8 mm(2)) compared with veins cultured without the antagonist (I:I+M, 0.29+/-0.02; lumen area, 2.5+/-0.7 mm(2); n=23) but were not significantly different from pre-cultured controls (I:I+M, 0.15+/-0.02; lumen area, 4.4+/-1.2 mm(2); n=17) (Dunn's test for non-parametric multiple comparisons: alpha<0.05). In organ bath experiments, ET-1 and 5-hydroxytryptamine constricted pre-cultured control vessels with pD(2) values (where pD(2) is defined as the negative logarithm of the molar EC(50) value of an agonist) of 8.9+/-0.4 and 7.0+/-0.4 (n=3) and E(max) (efficacy) values of 86+/-3% and 71+/-13% (compared with constriction induced by KCl) respectively. There was no difference in the responsiveness of veins cultured for 14 days to either agonist, indicating that the vessels maintained in organ culture remain viable. Crucially, vein segments cultured with 1 microM PD156707 (a concentration that antagonized ET-1 responses in pre-cultured control vessels) contracted to ET-1 with a potency comparable to that obtained in vessels cultured in the absence of the antagonist (pD(2)=8.9+/-0.4 and 8.0+/-0.6 respectively, n=3) confirming that PD156707 was not toxic to the tissue at the concentration used. In conclusion we have shown that the ET(A)-selective antagonist, PD156707, completely blocked intimal hyperplasia in human saphenous veins in organ culture, suggesting that ET(A) antagonists may be beneficial in preventing or delaying saphenous vein graft disease in patients receiving bypass grafts for coronary artery disease.

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Endothelin receptor expression and pharmacology in human saphenous vein graft

Cited by 27 publications

References 50 publications

Endothelin-1-induced responses in isolated mouse vessels: the expression and function of receptor types

Endothelin-1-induced responses in isolated mouse vessels: the expression and function of receptor types

Pressure-Induced Upregulation of Preproendothelin-1 and Endothelin B Receptor Expression in Rabbit Jugular Vein In Situ

ETA receptor antagonists inhibit intimal smooth muscle cell proliferation in human vessels

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