Endothelial factors in the cardiovascular system

The cardiovascular system is regulated by neuronal influences, circulating hormones as well as paracrine and autocrine mechanisms in the blood vessel wall. Endothelial factors play a primary role by releasing substances which can regulate vascular tone and structure as well as adhesion of circulating blood cells. Prostacyclin (PGI2) activates cAMP and is a vasodilator and platelet inhibitor function. Nitric oxide (NO) formed from L-arginine via the activity of endothelial NO synthase (eNOS). Platelets also express eNOS. eNOS is increased in its expression by shear stress and estrogen and possibly other factors. The L-arginine nitric oxide pathway also is stimulated by shear stress as well as receptor-operated mechanisms (i.e. acetylcholine, histamine, bradykinin, substance P, ATP/ADP and thrombin). NO acts as a vasodilator and platelet inhibitor via cGMP. Furthermore, endothelial cells produce constricting factors such as endothelin-1 (ET1), thromboxane A2 and prostaglandin H2. ET1 activates ETA- and ETB-receptors on vascular smooth muscle to cause contraction and endothelial ETB-receptors cause vasodilation (by NO and PGI2). In vascular smooth muscle cells, NO is an inhibitor and ET1 a stimulator of migration and proliferation. The endothelium is a target and mediator of cardiovascular disease and may exhibit profound dysfunction as cardiovascular disease progresses.