Influence of endothelin on human platelet aggregation and prostacyclin generation from human vascular endothelial cells in culture.

Kato, Kazuharu; Sawada, Shohei; Toyoda, Takeo; Kobayashi, Kyoichiro; Shirai, Kaoru; Yamamoto, Katsumi; Tamagaki, Toshiyuki; Yamagami, Masahito; Yoneda, Mitsuru; Takada, Osamu; Uno, Masashi; Tsuji, Hajime; Nakagawa, Masao

doi:10.1253/jcj.56.422

Cited by 10 publications

(3 citation statements)

References 21 publications

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“…The negative inotropic and relaxant effects of NO have largely been attributed to a cGMPmediated reduction in myofilament Ca 2ϩ responsiveness, via activation of PKG (60) and possibly subsequent phosphorilation of troponin I (31). ET-1 also stimulates the release of prostaglandins, namely, prostacyclin, as shown in bovine and human vascular endothelial cells (14,27) and in isolated (26) and in vivo rabbit hearts (59). Prostaglandins act through their specific receptors that are coupled via G proteins to second messenger systems, mainly cAMP and possibly inositol 1,4,5-trisphosphate (51).…”

Section: Discussionmentioning

confidence: 99%

Inotropic effects of ET_Breceptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins

Leite‐Moreira

Brás-Silva

2004

American Journal of Physiology-Heart and Circulatory Physiology

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Endothelin (ET)-1 acts on ETA and ETB receptors. The latter include ETB1 (endothelial) and ETB2 (muscular) subtypes, which mediate opposite effects on vascular tone. This study investigated, in rabbit papillary muscles (n = 84), the myocardial effects of ETB stimulation. ET-1 (10(-9) M) was given in the absence or presence of BQ-123 (ETA antagonist). The effects of IRL-1620 (ETB1 agonist, 10(-10)-10(-6) M) or sarafotoxin S6c (ETB agonist, 10(-10)-10(-6) M) were evaluated in muscles with intact or damaged endocardial endothelium (EE); intact EE, in the presence of NG-nitro-L-arginine (L-NNA); and intact EE, in the presence of indomethacin (Indo). Sarafotoxin S6c effects were also studied in the presence of BQ-788 (ETB2 antagonist). ET-1 alone increased 64 +/- 18% active tension (AT) but decreased it by 4 +/- 2% in the presence of BQ-123. In muscles with intact EE, sarafotoxin S6c alone did not significantly alter myocardial performance. Sarafotoxin S6c (10(-6) M) increased, however, AT by 120 +/- 27% when EE was damaged and by 39 +/- 8% or 23 +/- 6% in the presence of l-NNA or Indo, respectively. In the presence of BQ-788, sarafotoxin S6c decreased AT (21 +/- 3% at 10(-6) M) in muscles with intact EE, an effect that was abolished when EE was damaged. IRL-1620 also decreased AT (22 +/- 3% at 10(-6) M) in muscles with intact EE, an effect that was abolished when EE was damaged or in the presence of L-NNA or Indo. In conclusion, the ETB-mediated negative inotropic effect is presumably due to ETB1 stimulation, requires an intact EE, and is mediated by NO and prostaglandins, whereas the ETB-mediated positive inotropic effect, observed when EE was damaged or NO and prostaglandins synthesis inhibited, is presumably due to ETB2 stimulation.

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Section: Discussionmentioning

confidence: 99%

Inotropic effects of ET_Breceptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins

Leite‐Moreira

Brás-Silva

2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…In contrast to inhibition with ET-1 other studies show that ET-1 enhances platelet activation [88,95]. In vitro aggregability was studied in young men with predisposition to hypertension.…”

Section: Et-1 and Human Plateletsmentioning

confidence: 99%

“…The increased levels of ET-1 in the platelets of haemodialysed patients (13.8 ± 3.1 versus 7.9 ± 1.3 fmol/mg protein in normal individuals) may be partly responsible for their lower aggregation [94]. ET-1 can release NO and PGI 2 from endothelial cells; these mediators could then result in inhibited platelet aggregation [95].…”

Section: Et-1 and Human Plateletsmentioning

confidence: 99%

Endothelin-1 and Human Platelets

Jagroop¹,

Daskalopoulou²,

Mikhailidis³

2005

CVP

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There is conflicting evidence regarding the effect of endothelin-1 (ET-1) on platelets. Some studies show that ET-1 activates platelets, others show platelet inhibition with ET-1 and some studies did not detect an effect of ET-1. These conflicting results may be due to complex interactions between platelet ET(A) and ET(B) receptors. ET-1 antagonism may emerge as an important therapeutic strategy in the management of several vascular disorders. However, to date the only prescribed ET-1 antagonist is bosentan for pulmonary arterial hypertension. Bosentan is a 'dual' ET-1 antagonist (i.e. it acts on both ET(A) and ET(B) receptors). Whether this action involves an effect on platelets remains to be established. In this review some of the studies describing the effect of ET-1 on human platelets are discussed. Vascular diseases where ET-1 is implicated are also considered.

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Endothelin as a Proinflammatory Mediator

Filep

Hay

1999

Pulmonary Actions of the Endothelins

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Influence of endothelin on human platelet aggregation and prostacyclin generation from human vascular endothelial cells in culture.

Cited by 10 publications

References 21 publications

Inotropic effects of ET_Breceptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins

Inotropic effects of ET_Breceptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins

Endothelin-1 and Human Platelets

Endothelin as a Proinflammatory Mediator

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Influence of endothelin on human platelet aggregation and prostacyclin generation from human vascular endothelial cells in culture.

Cited by 10 publications

References 21 publications

Inotropic effects of ETBreceptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins

Inotropic effects of ETBreceptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins

Endothelin-1 and Human Platelets

Endothelin as a Proinflammatory Mediator

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Product

Resources

About

Inotropic effects of ET_Breceptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins

Inotropic effects of ET_Breceptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins