Cardiac and Renal Prostaglandin I2

Abstract

A B S T R A C T Both the isolated perfused rabbit heart and kidney are capable of synthesizing prostaglandin (PG) I2. The evidence that supports this finding includes: (a) radiochemical identification of the stable end-product of PGI2, 6-keto-PGF,l, in the venous effluent after arachidonic acid administration; (b) biological identification of the labile product in the venous effluents which causes relaxation of the bovine coronary artery assay tissue and inhibition of platelet aggregation; and (c) confirmation that arachidonic acid and its endoperoxide PGH2, but not dihomo-y-linolenic acid and its endoperoxide PGH, serve as the precursor for the coronary vasodilator and the inhibitor of platelet aggregation. The rabbit heart and kidney are both capable of converting exogenous arachidonate into PGI2 but the normal perfused rabbit kidney apparently primarily converts endogenous arachidonate (e.g., generated by stimulation with bradykinin, angiotensin, ATP, or ischemia) into PGE2; while the heart converts endogenous arachidonate primarily into PGI2. Indomethacin inhibition of the cyclo-oxygenase unmasks the continuous basal synthesis of PGI2 by the heart, and of PGE2 by the kidney. Cardiac PGI2 administration causes a sharp transient reduction in coronary perfusion pressure, whereas the intracardiac injection of the PGH2 causes an increase in coronary resistance without apparent cardiac conversion to PGI1. The perfuLsed heart rapidly degrades most of the exogenous endoperoxide probably into PGE2, while exogenous PGI2 traverses the heart without being metabolized. The coronary vasoconstriction produced by PGH2 in the normal perfused rabbit heart suggests that the endoperoxide did not reach the PGI2 synthetase, whereas

Shortening of the Bleeding Time in Rabbits by Hydrocortisone Caused by Inhibition of Prostacyclin Generation by the Vessel Wall

“…Vessel injury is normally associated with transient vasoconstriction which is followed by vessel relaxation. We suggest that the vessel relaxation after constriction is contributed to by smooth muscle-relaxing prostaglandins that are released from the vessel wall in response to injury (27)(28)(29), and that the inhibition of the synthesis of these prostaglandins leads to a sustained vasoconstriction. This vasoconstriction has a hemostatic effect when the vessel wall in either normal or thrombocytopenic animals is damaged, or the vessels in the microcirculation transected.…”

Rapid inactivation of cyclooxygenase activity after stimulation of intact platelets

“…DISCUSSION The involvement of phospholipases A2 in prostaglandin biosynthesis by intact cells has been suggested for many years. Free fatty acid levels are very low in most tissues, and phospholipase activation is believed to be required for prostaglandin biosyn- thesis (1,5,16,(19)(20)(21)(22). This activation can be brought about in different tissues through a variety of stimuli, such as bradykinin, angiotensin II, vasopressin, thrombin, collagen, serum, ionophore A23187, and trypsin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(19)(20)(21)(22).…”

Eighth Gaddum Memorial Lecture University of London Institute of Education December 1980: Biological Importance of Prostacyclin

“…Undisturbed endothelial cell monolayers can also readily transform PGH2 to prostacyclin (Marcus, Weksler & Jaffe, 1978). However, the hypothesis was challenged by Needleman and associates (Needleman, Bronson, Wyche, Sivakoff & Nicolaou, 1978) who demonstrated that, while arachidonic acid was rapidly converted to prostacyclin by perfused rabbit hearts and kidneys, PGH2 was not readily transformed. They concluded that some degree of vascular damage was necessary for the endoperoxide to be utilized by prostacyclin synthetase.…”