Endothelial nitric oxide, prostacyclin (PGI2) and tissue plasminogen activator (t-PA): alliance or neutrality?
In vivo a powerful triad of endothelial secretogogues regulates thrombo-resistance and vascular tone. In physio-pathological circumstances stimulation of endothelial receptors (purinergic, muscarinic, kinin) releases prostacyclin (PGI2), nitric oxide (NO) and tissue plasminogen activator (t-PA) in a coupled manner. Alliance between them occurs at level of protection against deposition of thrombi over the vascular wall. Activation of fibrinolysis by t-PA through generation of plasmin is complemented with multifactorial desactivation of platelets by PGI2 and a selective inhibition of release of plasminogen activator inhibitor-1 (PAI-1) from platelets by NO. This concerted action of the triad leads to increase in anti-thrombotic and thrombolytic potentials. Administrated separately t-PA (or streptokinase) and PGI2 (or iloprost) produce unwanted effects such as "paradoxic thrombogenesis" or "rebound activation of platelets", respectively. It is because they are missing a natural ally. On the other hand, endothelial regulation of vascular tone depends on NO, exclusively. Only exogenous PGI2 is hypotensive, and even then it does not synergize with NO. In vitro all types of interactions between PGI2 and NO occur. For instance, synergism--in platelets, addition--in vascular smooth muscle and antagonism--in macrophages. Activity of arachidonate cyclooxygenase is claimed to be either stimulated or inhibited by NO. A transfer of conclusions from in vitro data to living systems must be very cautious.
Gryglewski
R J
RJ
Department of Pharmacology, Medical College of Jagiellonian University, Kraków, Poland.
D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000502:physiology*; D006801:Humans; D009420:Nervous System / Q000378:metabolism; D009424:Nervous System Physiological Phenomena; D009569:Nitric Oxide / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000502:physiology*
D009569:Nitric Oxide; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator