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

Abstract

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.

C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression

“…6). The potency of CNP was akin to that reported for NO released by isolated vascular endothelial cells (23,24) and fits with the reported ability of CNP to block thrombus formation (25).…”

“…CNP (0.1-1 M) was superfused for 10 min, and leukocyte flux was recorded. To investigate the involvement of the NPR-C in responses to CNP, the ability of the selective NPR-C agonist (17), cANF [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] (1 M) to inhibit leukocyte rolling was also explored.…”

Modulation of the vasodepressor actions of acetylcholine, bradykinin, substance P and endothelin in the rat by a specific inhibitor of nitric oxide formation

“…Since EDRF has been now characterized both biologically and chemically in a variety of systems as NO Hutchinson et al, 1987;Radomski et al, 1987;Ignarro et al, 1987, Khan & Furchgott, 1987Moncada et al, 1988;Kelm et al, 1988), whose synthesis can be inhibited by L-NMMA (Palmer et al, 1988b;Rees et al, 1989a,b) the current findings with L-NMMA in the rat further implicate endothelium-derived NO in the regulation of cardiovascular tone and blood pressure, and as a mediator of the hypotensive actions of endogenous endothelium-dependent vasodilators in vivo. The modulation of local substrate levels and enzymic activity involved with the biosynthesis of NO in the vascular endothelium may, therefore, make an important contribution to the physiological regulation and pathological conditions of the cardiovascular system.…”

Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection

“…It has been demonstrated that NO is destroyed by superoxide anions and that inactivation of superoxide anions protects and prolongs the action of NO Moncada et al, 1986;Rubanyi & Vanhoutte, 1986). Thus, superoxide dismutase induces relaxation of rat aortic strips with intact endothelium (Rubanyi & Vanhoutte, 1986;Rimele et al, 1988) and increases the antiaggregatory activity of neutrophils (Radomski et al, 1987). Compounds with steroidal structures were recently shown to be potent O-scavengers and to be active in protecting neurones against peroxide injury (Hall et al, 1987).…”