Interactions Between Endothelial Secretogogues

Abstract

Among endothelial secretogogues prostacyclin (PGI₂), nitric oxide (NO) and tissue plasminogen activator (t-PA) play a crucial role in maintaining thromboresistance, tone and structure of the vascular wall. Most receptor agonists, such as B₂ kinin receptor agonists, or shear force produce a coupled release of all three secretogogues, and therefore interactions between them are to be expected. Essentially, PGI₂ is a platelet suppressant, NO a vasodilator and t-PA a fibrinolytic agent. These and other properties of endothelial secretogogues supplement each other in protecting the cardiovascular system from injuries. It is not surprising that disturbances of the secretory function of endothelial cells are associated with atherosclerosis, diabetes, thrombosis or hypertension. Traditionally, PGI₂, NO, t-PA or their substitutes are used individually for the treatment of peripheral arterial disease, angina pectoris or acute myocardial infarction. In light of recent findings, their joint administration can be advocated. For instance, NO donors will potentiate platelet-suppressant action of PGI₂ analogues, whereas exogenous PGI₂ or TXA₂ synthase inhibitors (i.e. following increase in endogenous PGI₂) will abolish a paradox of prothrombotic action of t-PA or streptokinase. The replacement therapy with PGI₂, NO or t-PA should match as closely as possible the physiologically coupled release of these secretogogues.

Key Words:

• prostacyclin
• nitric oxide
• NO donors
• tissue plasminogen activator
• streptokinase
• endothelium
• thrombolysis
• thrombogenesis
• platelets
• fibrinolysis
• interactions