Prostaglandins, prostacyclin, and thromboxane in cardiovascular diseases

Abstract

Chan, P.S., and P. Cervoni: Prostaglandins, prostacyclin, and thromboxane in cardiovascular diseases. Drug Dev. Res. 7:341-359, 1986. Prostaglandins appear to play an important role in or to be found therapeutically useful in various cardiovascular diseases, such as hypertension, arrhythmias, ventricular fibrillation, arterial thrombosis, myocardial ischemia, myocardial infarction, certain types of angina pectoris, atherosclerosis, circulatory shock, and peripheral arterial diseases, etc. Prostacyclin and prostaglandins El, E2, and D2 are considered beneficial, while thromboxane A2 and prostaglandin FpU are considered harmful and their formations should be inhibited. Inhibition of the formation of the vasodepressor prostaglandins, such as prostacyclin and prostaglandin E2, in humans and animals leads to increase in arterial blood pressure and total peripheral resistance as well as to decrease the efficacy of most antihypertensive drugs, which suggests that these vasodepressor prostaglandins play an important role in hypertension. Most prostaglandins exert antiarrhythmic activity. Prostacyclin and thromboxane synthetase inhibitors are particularly effective in myocardial infarctionlreperfusioninduced arrhythmias and ventricular fibrillation (sudden cardiac death) where the classical antiarrhythmic agents are not very effective. Prostacyclin and thromboxane synthetase inhibitors are effective in reducing myocardial infarct size, increasing coronary blood flow, and inhibiting arterial thrombosis. Atheroclerosis may result from decrease in prostacyclin formation in the blood vessel wall due to inhibition by the high concentration of lipid peroxides in the blood. Prostacyclin stimulates cholesterol ester hydrolase, the enzyme that converts cholesterol ester to free cholesterol for mobilization out of the cells. PGE2 inhibits acyl CoA cholesterol-0-acyltransferase (ACAT), the enzyme that catalyzes the reesterification of free cholesterol. Therefore, prostacyclin, PGE2, and their stable analogs may be useful for the prevention and induction of regression of atherosclerosis. Prostacyclin, PGE1, and other stable prostaglandin analogs, such as iloprost and viprostol, have Received final version December 20, 1985; accepted February 20, 1986 342Chan and Cervoni been reported to be beneficial for the treatment of peripheral arterial diseases. It is very likely that new drugs that affect the prostaglandin systems will be introduced for the prevention and treatment of various cardiovascular diseases in the very near future.

Sexual dimorphism in prostanoid-potentiated vascular contraction: roles of endothelium and ovarian steroids

“…Before this study, constrictor prostanoids were not believed to play a significant role in the regulation of normal vascular tone, except in the pulmonary circulation. The findings of the present study are important because the current dogma surrounding the literature states that vascular TxA 2 production is important only in pathophysiological states such as hypertension in males, but not in normal states or in females (8,40,41). This study clearly establishes that constrictor prostanoids play an important role in the regulation of vascular tone in the normal systemic female vasculature.…”

“…The possibility that constrictor prostanoids may potentiate vasoconstrictor responsiveness of the systemic vasculature in females is of particular interest because it is generally accepted that constrictor prostanoids, while important in pathological states such as hypertension (40), play little or no role in the regulation of normal vascular tone (8,41) except in the pulmonary vasculature (7,18,59,61). Furthermore, epidemiological evidence that the incidences of primary vascular diseases involving excessive vasoconstriction are severalfold higher in premenopausal women than in men (11,24,60,63) suggests that a common mechanism of vasospasm, which may involve constrictor prostanoids, may be responsible (5,10,17,19,64).…”

Expression discordance of monozygotic twins at birth: Effect of intrauterine environment and a possible mechanism for fetal programming

“…Prostaglandins also play an important role in cardiovascular diseases such as hypertension, myocardial infarction, arrhythmias, angina and in asthma. [69][70][71] An association with cardiovascular function or disease was further revealed by pathway analysis (Sup. The RNA bound to the column was washed with 700 μl Buffer RW1 by centrifuging at 8,000 g and repeated twice with 500 μl Buffer RPE.…”

Current concepts and animal models of sudden cardiac death for drug development

“…Another thromboxane synthetase inhibitor, CV-415 1 , was also found to be effective [Imamoto et al, 19861. It appears that any agent that either increases prostacyclin formation or decreases thromboxane formation will be effective [see Chan and Cervoni, 1986;Parratt et al, 19871. Others [Burke et al, 1982;Kramer et al, 1985) have disputed the involvement of thromboxane A, in reperfusion-induced VF.…”