Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium.
The endothelium lines the luminal surface of every blood vessel, allowing it contact with 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 prostacyclin (IP) receptors and/or intracellular peroxisome proliferator-activated receptors (PPAR) beta. 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, PPAR beta and guanylyl cyclase pathways in vessels and platelets, is discussed.
Mitchell
Jane A
JA
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK. j.a.mitchell@ic.ac.uk
Ali
Ferhana
F
Bailey
Lucy
L
Moreno
Laura
L
Harrington
Louise S
LS
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D001808:Blood Vessels / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006728:Hormones / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D006728:Hormones; D009569:Nitric Oxide; D011464:Epoprostenol