Study of tachyphylaxis to the vasoconstrictor effect of arachidonic acid in the isolated perfused kidney of the rat.
The isolated perfused kidney of the rat was used to address the development of tachyphylaxis to the vasoconstrictor effects of arachidonic acid. Repeated administration of arachidonic acid (3 micrograms at 10-min intervals) to the isolated kidney of the rat, perfused in situ with Krebs-Henseleit solution, led to the development of tachyphylaxis to the renal vasoconstrictor effects of arachidonic acid, using perfusion pressure changes as an index. Vasoconstrictor responses to either angiotensin or the endoperoxide analog, U46619, were unaffected by repeated administration of arachidonic acid. Associated with progressively reduced renal vasoconstrictor responses to arachidonic acid were parallel decrements in the renal venous release of prostanoids, measured by radioimmunoassay. In contrast, the release of prostanoids from the kidney stimulated by angiotensin II was increased after repeated administrations of arachidonic acid. These data suggest that the sequential reduction in renal vasoconstrictor responses to arachidonic acid is due to diminished conversion to prostaglandins, possibly due to inactivation of cyclooxygenase, decreased entry of arachidonic acid into the cell or its increased esterification into phospholipids.
Quilley
J
J
Department of Pharmacology, New York Medical College, Valhalla.
McGiff
J C
JC
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013618:Tachyphylaxis; D013929:Thromboxane B2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D001095:Arachidonic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D000804:Angiotensin II; D016718:Arachidonic Acid; D013929:Thromboxane B2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid