Renal vascular responses and eicosanoid release in diabetic rats.
Changes in renal perfusion pressure and eicosanoid release in response to arginine vasopressin (AVP; 1-10 ng) and angiotensin II (ANG II; 1-10 ng) were determined 5 days, 2 wk, and 8-12 wk after the induction of diabetes with streptozotocin (STZ) in male Wistar rats. Renal perfusion pressure responses to AVP and ANG II were reduced at 2 and 8-12 wk, but not at 5 days, after the induction of diabetes. However, AVP- and ANG II-stimulated release of prostaglandins into the renal venous effluent was depressed at all times tested. Inhibition of cyclooxygenase with indomethacin did not significantly influence the perfusion pressure responses to ANG II and AVP. Likewise, raising perfusate glucose levels to 400 mg/dl or adding insulin (180 microU/ml) to the perfusate failed to modify responses to ANG II. In contrast, administration of 0.3 microgram arachidonic acid (AA), a dose approaching threshold in control rat kidneys, to the kidney of the diabetic rat resulted in a marked increase in perfusion pressure. Associated with the increase in renal perfusion pressure to AA in the diabetic rat were significant increases in renal venous efflux of prostaglandin E2 and prostacyclin compared with control. These data suggest a defect in renal deacylation-reacylation of AA associated with an increase in cyclooxygenase activity in the diabetic rat.
Sarubbi
D
D
Department of Pharmacology, New York Medical College, Valhalla 10595.
McGiff
J C
JC
Quilley
J
J
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D001808:Blood Vessels / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D015777:Eicosanoids / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D013311:Streptozocin; D013997:Time Factors
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D007328:Insulin; D000804:Angiotensin II; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; D013311:Streptozocin; D005947:Glucose