Selective inhibition of thromboxane synthesis partially protected while inhibition of angiotensin II formation did not protect rats against acute renal failure induced with glycerol.
Acute renal failure (ARF) was induced in 35 week-old conscious female Wistar rats, by intramuscular (IM) injection of glycerol. Intraperitoneal (IP) injection of imidazole, an inhibitor of thromboxane (TXA2) synthesis, partially protected the animals against ARF. This protection was accompanied by a significant decrease in renal TXB2 (the stable chemical metabolite of TXA2) and a significant increase in renal 6-keto-PGF1 alpha (the stable chemical metabolite of PGI2) synthesis. Intraperitoneal injection of captopril (SQ 14225) an angiotensin-converting-enzyme inhibitor, did not protect the animals against ARF. This lack of protection was accompanied by a significant increase in renal TXB2 and a significant decrease in renal 6-keto-PGF1 alpha synthesis. The results suggest that: (a) the renin-angiotensin (R-A) system does not play a role, or has only a secondary one in the development of ARF; (b) thromboxane A2 (the most potent vasoconstrictor and platelet aggregator agent known) is the preponderant agent responsible for the development of this pathological syndrome.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D015232:Dinoprostone; D005260:Female; D005990:Glycerol; D007093:Imidazoles / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000652:urine; D051381:Rats; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000652:urine; D013931:Thromboxanes / Q000096:biosynthesis*
D007093:Imidazoles; D011453:Prostaglandins; D011458:Prostaglandins E; D013931:Thromboxanes; D000804:Angiotensin II; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C029899:imidazole; D002216:Captopril; D015232:Dinoprostone; D005990:Glycerol