Roles of prostanoids in the pathogenesis of cardiovascular diseases

The roles of prostanoids in the pathogenesis of cardiovascular diseases and in the development of pathological conditions have been examined using mice lacking the individual, specific prostanoid receptor. Prostaglandin (PG) I-2 protected the heart from ischemia-reperfusion injury in a model of acute myocardial infarction. In addition, PGI(2) suppressed the development of pressure overload-induced cardiac hypertrophy. Aside from its potent vasodilatory action, PGI(2) contributed critically to the development of renovascular hypertension via the activation of the renin-angiotensin-aldosterone system. Thromboxane (TX) A(2) and PGF(2)alpha were found to be the mediators of inflammatory tachycardia under a systemic inflammatory condition induced by lipopolysaccharide. Under a septic condition leading to a vascular hypo-responsive state, TXA(2) worked to maintain vascular tone by inhibiting the induction of inducible nitric oxide synthase in vascular smooth muscle cells. Mice lacking the PGE(2) receptor subtype EP3 had a bleeding tendency and were resistant to thromboembolism, due to a defective activation of platelets. From these studies, the important and novel roles of prostanoids in the pathogenesis of cardiovascular diseases have been clarified. [Int Angiol 2010;29(Suppl. 1 to No 2):19-27]