Endothelin‐1 inhibits platelet aggregation in vivo: a study with ¹¹¹indium‐labelled platelets

Abstract

A non‐invasive technique for the scintigraphic determination of 111indium‐labelled platelet aggregation stimulated with submaximal doses of adenosine diphosphate (ADP, 56 μg kg−1 i.v.), collagen (100 μg kg−1 i.v.), platelet‐activating factor (PAF, 0.1 μg kg−1 i.v.) or thrombin (18 iu kg−1 i.v.) was used to investigate the platelet‐inhibitory effects of endothelin 1 (ET‐1) in anaesthetized rabbits in vivo. ET‐1 (1 nmol kg−1 i.v.) inhibited ADP‐stimulated platelet aggregation in vivo; a maximum inhibition of 78% of the control value was reached at 3 min, with 45% inhibition at 15 min, and a return to control values at 30 min after injection of the peptide. ET‐1 (1 nmol kg−1 i.v.) inhibited in vivo platelet aggregation in response to collagen or PAF by 86% and 52%, respectively, but had no effect on thrombin‐induced platelet aggregation. Indomethacin (5 mg kg−1 i.v.) abolished the ET‐1‐induced inhibition of ADP‐stimulated platelet aggregation and significantly potentiated and prolonged the pressor response brought about by ET‐1. In conclusion, the data demonstrate that ET‐1 potently inhibits platelet aggregation in the anaesthetized rabbit in vivo by releasing a hypotensive and anti‐aggregatory cyclo‐oxygenase product, presumably prostacyclin, into the circulation.

Effects of prolonged tourniquet ischaemia and short-term venous stasis on plasma endothelin-1 levels in man

“…Another substance released from endothelial cells during venous stasis is tissue plasminogen activator, which acts to balance interactions between the coagulation and fibrinolytic systems by promoting fibrinolysis [ 2 3 ] . Although ET-1 may be antithrombotic by causing release of prostacyclin from endothelial cells [24], the possible role of ET-1 in regulating thrombotic and coagulant activities of the endothelium is largely unknown.…”

The role of nitric oxide as an endogenous regulator of platelet and neutrophil activation within the pulmonary circulation of the rabbit

“…"'Indium-labelling ofplatelets Details of this procedure for rabbit platelets have been described elsewhere Thiemermann et al, Author for correspondence. 1990).…”

“…The present experiments were therefore performed to test the hypothesis that NO is an endogenous regulator of the function of formed blood elements within the vasculature. To this end, use has been made of L-NG-nitro arginine methyl ester (L-NAME), a potent and selective inhibitor of vascular and non-vascular NO biosynthesis ; Moore et al, 1990) on in vivo platelet and neutrophil aggregation in the pulmonary (Page et al, 1982;Thiemermann et al, 1990) and cerebral ) vascular beds of anaesthetized rabbits; a non-invasive technique for the determination of in vivo platelet aggregation with "'indiumlabelled platelets was used.…”

Endothelin‐1‐induced myocardial ischaemia and oedema in the rat: involvement of the ETA receptor, platelet‐activating factor and thromboxane A2

“…Another possibility might be that ET-1 is less active in releasing vasodilator prostaglandins in conscious than pithed rats, and consequently prostaglandins might be more important in limiting the pressor effects of ET-1 in pithed than conscious rats. The observations that cyclo-oxygenase inhibitors can attenuate the depressor response to ET-1 in anaesthetized dogs (Herman et al, 1989), and either inhibit or potentiate the pressor action of ET-1 in anaesthetized guinea-pigs (Whittle et al, 1989) or rabbits (Thiemermann et al, 1990;Rogerson et al, 1993), respectively, indicate important species differences in the mechanisms mediating the vascular actions of ET-1. It is uncertain at present which receptor subtypes mediate the ET-1-induced release of vasodilator prostanoids in the rat.…”