Renal vascular responsiveness to arachidonic acid in experimental diabetes.
1. Isolated perfused kidneys from diabetic rats (duration 4-6 and 20-24 weeks) were more sensitive to the vasoconstrictor effects of arachidonic acid than kidneys from age-matched control rats. Sensitivity diminished with age in both control and diabetic groups. 2. The enhanced vasoconstrictor effect of arachidonic acid in diabetic rat kidneys was associated with increased conversion to prostaglandins. 3. The renal vasoconstrictor response to arachidonic acid in both groups was reduced by thromboxane A2/prostaglandin H2 receptor antagonism but not by inhibition of thromboxane synthase. 4. Diabetic rat kidneys were also more sensitive to the vasoconstrictor effects of the endoperoxide analogue, U46619, while vasoconstrictor responses to phenylephrine were not markedly different from those of control rat kidneys. 5. In conclusion, prostaglandin endoperoxides appear to mediate arachidonic acid-induced vasoconstriction in diabetic and control rat kidneys. The enhanced renal vasoconstrictor response to arachidonic acid in diabetic rats results from increased sensitivity to endoperoxides and increased formation of endoperoxides from arachidonic acid.
Quilley
J
J
Dept. Pharmacology, New York Medical College, Valhalla 10595.
McGiff
J C
JC
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015232:Dinoprostone / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011449:Prostaglandin Endoperoxides / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000378:metabolism
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D010656:Phenylephrine; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015232:Dinoprostone