PGI2 effects

Reproductive System. The primary PGs are intimately involved in reproductive physiology (67). PGE2 and PGP2Q, are potent contractors of the pregnant utems and intravenous infusion of either of these compounds to pregnant humans produces a dose-dependent increase in frequency and force of uterine contraction. PGI2 and TXA2 have mild relaxant and stimulatory effects, respectively, on uterine tissue. The primary PGs also play a role in parturition, ovulation, luteolysis, and lactation and have been impHcated in male infertility. 

In this study we incorporated PGEj and a PGI2 derivative into lipid microspheres, and the tissue distribution and clinical effectiveness of these lipo-preparations were studied. 

Lipo-PGI2. Prostacyclin (PGI2) is more potent than PGEj in antiplatelet and antithrombotic effects, and is expected to be very useful in the treatment of various thrombotic diseases (70,77). However, it causes more adverse reactions, such as hypotension and facial flushes, because of its vasodilation and possible suppression of feed-back mechanisms. Many attempts at clinical applications have failed. We have conducted studies on methylated TEI9090 (Figure 2), a chemically stable and... 

Of the various pharmacological actions of PGEj and PGI2, one action which has not yet been studied intensively, but seems to be important for the treatment of arteriosclerotic diseases, is their effect on vascularization. This suggests the need to determine if lipid microspheres accumulate at the site of vascularization. We are now conducting a study to investigate this possibility. Since the space between endothelial cells in new blood vessels is as big as that of vessels with sclerosis or inflammation, lipid microspheres are very likely to accumulate in new blood vessels. Figure 4 shows a schema of the distribution and accumulation of lipid microspheres at the site of vascular lesions. 

Another metabolite of arachidonic acid is prostacyclin (PGI2). As with TxA2, PGI2 is produced continuously. Synthesized by vascular smooth muscle and endothelial cells, with the endothelium as the predominant source, PGI2 mediates effects that are opposite to those of TxA2. Prostacyclin causes vasodilation and inhibits platelet aggregation and, as a result, makes an important contribution to the antithrombogenic nature of the vascular wall. 

The author next tried to stabilize the PGI2 structure by introducing second fluorine atom to the 7-position. However, it had been unknown to make such a difluorovinyl ether unit in the literature. We studied difluorination and Wittig reaction as key steps in the synthetic route of the target difluoro-PGl2 from the Corey lactone. After searching the difluorination reaction, it was found that fluorination with A/-fluorobenzenesulfonimide in the presence of potassium bis(trimethylsilyl) amide and manganese dibromide effectively provided the desired difluoride (Table 7) [106]. 

Renal system PGE, PGE PGI2 increase glomerular filtration through their vasodilatory effects and increase water sodium excretion. 

Kinins produce marked vasodilation in several vascular beds, including the heart, kidney, intestine, skeletal muscle, and liver. In this respect, kinins are approximately 10 times more potent on a molar basis than histamine. The vasodilation may result from a direct inhibitory effect of kinins on arteriolar smooth muscle or may be mediated by the release of nitric oxide or vasodilator prostaglandins such as PGE2 and PGI2. In contrast, the predominant effect of kinins on veins is contraction again, this may result from direct stimulation of... 

There is an additional layer of complexity associated with the effects of renal prostaglandins. In contrast to the medullary enzyme, cortical COX-2 expression is increased by low salt intake, leading to increased renin release. This elevates glomerular filtration rate and contributes to enhanced sodium reabsorption and a rise in blood pressure. PGE2 is thought to stimulate renin release through activation of EP4 or EP2. PGI2 can also stimulate renin release and this may be relevant to maintenance of blood pressure in... 

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