Received June 11, 2007
Revised August 20, 2007
Accepted after revision September 21, 2007

¹ Imperial College, UK

^* To whom correspondence should be addressed. E-mail: j.a.mitchell{at}ic.ac.uk.

	Abstract

The endothelium lines the luminal surface of every blood vessel allowing it to contact circulating blood elements as well as the underlying vascular smooth muscle layer. In healthy vessels the endothelium expresses constitutive forms of nitric oxide synthase (NOSIII) and cyclo-oxygenase (COX-1) which produce the vasoactive hormones NO and prostacyclin respectively. Both NO and prostacyclin relax blood vessels and inhibit platelet activation. The actions of prostacyclin are mediated by cell surface IP and/or intracellular PPAR receptors. The actions of NO are mediated predominately by activation of intracellular guanylyl cyclase leading to the formation of cGMP. In platelets the actions of NO and prostacyclin are synergistic, but in vessels their actions are additive. In diseased vessels inducible forms of NOS (NOSII) and cyclo-oxygeanse (COX-2) are expressed in vascular smooth muscle resulting in the release of large amounts of NO, prostacyclin and prostaglandin E2. The relative contribution of NOSII and COX-2 to vascular inflammation is still debated, but is likely to result in both protective and damaging responses. The relative contribution of constitutive forms of NOS and COX as well as interactions between IP, peroxisome proliferator-activated receptors (PPAR) and guanylyl cyclase pathways in vessels and platelets will be discussed.

Key Words: Endothelium, Nitric oxide, Prostacyclin