Endothelium‐dependent inhibition of platelet aggregation

1,082

461

1 The interactions between endothelium-derived nitric oxide (NO) and prostacyclin as inhibitors of platelet aggregation were examined. 2 Porcine aortic endothelial cells treated with indomethacin and stimulated with bradykinin (10-100 nM) released NO in quantities sufficient to account for the inhibition of platelet aggregation attributed to endothelium-derived relaxing factor (EDRF). 3 In the absence of indomethacin, stimulation of the cells with bradykinin (1-3 nM) released small amounts of prostacyclin and EDRF which synergistically inhibited platelet aggregation. 4 EDRF and authentic NO also caused disaggregation of platelets aggregated either with collagen or with U46619. 5 A reciprocal potentiation of both the anti-and the dis-aggregating activity was also observed between low concentrations of prostacyclin and authentic NO or EDRF released from endothelial cells. 6 It is likely that interactions between prostacyclin and NO released by the endothelium play a role in the homeostatic regulation of platelet-vessel wall interactions.

Section: Discussionmentioning

confidence: 99%

“…EDRF also inhibits platelet aggregation (Azuma et al, 1986;Furlong et al, 1987;Radomski et al, 1987). We have recently demonstrated that nitric oxide (NO) is released by vascular endothelial cells in amounts sufficient to account for the vasodilator properties of EDRF .…”

Section: Introductionmentioning

confidence: 99%

The anti‐aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide

Radomski

Palmer

Moncada

1987

1,082

461

“…Endothelium-derived relaxing factor (EDRF) mediates the vasodilator effect of acetylcholine (ACh) and a number of other substances on isolated blood vessels (Furchgott, 1984) and exhibits potent platelet anti-aggregatory activity both in vitro (Azuma et al, 1986) and in vivo Hogan et al, 1988). Evidence has been presented in the literature that EDRF is identical with nitric oxide (NO) (Palmer et al, 1987) and is formed from L-arginine (Palmer et al, 1988a).…”

Section: Introductionmentioning

confidence: 96%

l‐N^G‐nitro arginine (l‐NOARG), a novel, l‐arginine‐reversible inhibitor of endothelium‐dependent vasodilatation in vitro

Moore

al-Swayeh

Chong

et al. 1990

740

377

1 The effect of L-NG-nitro arginine (L-NOARG) was compared with that of L-NG-monomethyl arginine (L-NMMA) on vasodilatation of the isolated aorta of the rabbit and perfused mesentery of the rat in response to acetylcholine (ACh) and sodium nitroprusside (NP). 2 L-NOARG (1.5-100Mm) and L-NMMA (3-100Mm) produced concentration-related contraction of the rabbit aorta precontracted with phenylephrine (700-900nM). Similarly, L-NOARG (10-2001pM) and L-NMMA (30-100 gM) elevated perfusion pressure of the noradrenaline (NA, 0.6-2.5mM)-preconstricted rat mesentery preparation. 6 These results identify L-NOARG as a potent, L-arginine reversible inhibitor of endothelium-dependent vasodilatation. The available data suggests that L-NOARG, like L-NMMA, inhibits endothelial nitric oxide (NO) biosynthesis.

“…The vascular relaxation induced by EDRF is mediated by the stimulation ofsoluble guanylate cyclase and the consequent rise in guanosine 3': 5'-cyclic monophosphate (cyclic GMP) levels (Rapoport et al, 1983). EDRF has also been reported to inhibit platelet aggregation (Azuma et al, 1986;Furlong et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Comparative pharmacology of endothelium‐derived relaxing factor, nitric oxide and prostacyclin in platelets

Radomski

Palmer

Moncada

1987

787

295

The pharmacological effects of endothelium‐derived relaxing factor (EDRF), nitric oxide (NO) and prostacyclin on human and rabbit platelets were examined. EDRF is released from porcine aortic endothelial cells, cultured on microcarriers and treated with indomethacin, in sufficient quantities to inhibit platelet aggregation induced by 9,11‐dideoxy‐9α,11α‐methano epoxy‐prostaglandin F2α (U46619) and collagen. The anti‐aggregating activity of EDRF was potentiated by M&B 22948, a selective inhibitor of cyclic GMP phosphodiesterase, and by superoxide dismutase (SOD) and was inhibited by haemoglobin and Fe2+. Both NO and prostacyclin inhibited platelet aggregation. The anti‐aggregatory activity of NO, but not that of prostacyclin, was potentiated by M&B 22948 and by SOD and was inhibited by haemoglobin and Fe2+. Thus NO is a potent inhibitor of platelet aggregation whose activity on platelets mimics that of EDRF. It is likely that the inhibitory effect of NO on platelets represents the action of endogenous EDRF and therefore this substance, together with prostacyclin, is a regulator of platelet‐vessel wall interactions.