Prostaglandins and the renin angiotensin system in canine endotoxemia

P. C. Isakson, F. Shofer, R. C. McKnight, R. A. Feldhaus, A. Raz, P. Needleman

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Administration of endotoxin to dogs caused a rapid initial decline in blood pressure followed by a transient recovery preceding death. Plasma renin activity was elevated 5 minutes after endotoxin administration and continued to rise throughout the course of shock. Indomethacin given 60 minutes after endotoxin caused an elevation of blood pressure and a 50% decrease in plasma renin activity. Pretreatment with indomethacin markedly attenuated both the hemodynamic changes and the rise in plasma renin activity caused by endotoxin administration. Prostaglandin (PG) E-like material was observed in renal venous blood 30 minutes after endotoxin administration and was abolished by indomethacin. In addition, a non-PG substance was found in dialysate from both arterial and renal venous blood within 5 minutes of endotoxin administration. Renal and mesenteric angiograms were taken at various stages of shock. Endotoxin administration caused a substantial increase in the diameter of intrarenal arterial branches which was temporally associated with the appearance of PGE-like material in the renal venous effluent. The mesenteric arteries were initially and transiently constricted by endotoxin and then were markedly and chronically dilated. Indomethacin simultaneously abolished renal PG and decreased renal and mesenteric arterial diameter.

Original languageEnglish
Pages (from-to)614-622
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
StatePublished - 1977


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