Prostaglandins, their intermediates and precursors: cardiovascular actions and regulatory roles in normal and abnormal circulatory systems

Abstract

The characterization of newly found unstable metabolites of arachidonic acid has provided new perspectives for cardiovascular regulatory mechanisms and new insights into disorders of the circulatory system. Since these intermediates are often more potent on and more specific for cardiovascular structures than the classical prostaglandins, they are more likely candidates as physiologic mediators of circulatory events. Their instability in vitro need not preclude these roles; on the contrary, the limited pharmacology described to date suggests that they function purely as local hormones. As such, changes in the rate of generation of these unstable but potent compounds would provide an excellent control system. The stable prostaglandins may represent only overflow of degradation products of the active mediators associated with pathologic events. For example, the dicovery of prostacyclin and the realization that this prostaglandin and not PGE2 is the primary metabolite of arachidonic acid in blood vessels emphasizes the need to reinterpret many of the previously held hypotheses that proposed that prostaglandins of the E series contributed to the regulation of vessel tone and blood pressure, Moreover, the contribution made by abnormal prostaglandin mechanisms to hypertensive disease should now take into account that a deficiency of prostacyclin and not PGE2 could be a major factor causing the elevated tension developed in vascular smooth muscle and the augmented vessel responsiveness to stimuli associated with hypertension.