前列腺素与血压调节-管又飞（2012-04-12华西医科大学）.pptVIP

* To date, many direct vascular mechanisms have been proposed. TZD PPARg agonists may lower blood pressure through inhibiting vasoconstrictive TXA2, endothelin-1 and angiotensin II signaling and enhancing vaso-relaxant EETs and prostacyclin production. * Okay, I hope in the past hour I have convinced you that …. * * Taken together, the present data suggest that the EP2 receptor predominates over the other EP subtypes in the vasculature - responding to PGE2 by conferring a vasodilatory effect. In the knockout mice, the absence of the EP2 receptor unmasks populations of vasoconstrictor EP receptors to shift the balance to a vasoconstrictive response to PGE2. * * * * * Taken together, the present data suggest that the EP2 receptor predominates over the other EP subtypes in the vasculature - responding to PGE2 by conferring a vasodilatory effect. In the knockout mice, the absence of the EP2 receptor unmasks populations of vasoconstrictor EP receptors to shift the balance to a vasoconstrictive response to PGE2. * * * Differential regional distribution of these receptor mRNAs is also seen by in situ hybridization. The left panel shows the EP1 receptor predominates in the papillary collecting duct, while the EP3 receptor predominates in the medullary thick limb, outer medullary and cortical collecting ducts. Several groups have generated mice with genetic disruption of these and, all the other prostanoid receptors, and Based on the mRNA expression and potent inhibitory effects of PGE2 on transport in these segments, significant renal phenotypes would seem likely. However, to paraphrase Aldus Huxley, nothing in science is more tragic than when a beautiful theory is destroyed by an ugly fact, and studies of these knockouts has provided significant surprises. * * * Figure 2. Baseline blood pressure levels in EP3 WT and KO mice. A) mean arterial blood pressure (MAP) levels in anesthetized EP3 WT (n=25) and KO mice (n=28). MAP was measured using the carotid arterial c