Depressed arteriolar responsiveness to norepinephrine in streptozotocin-induced diabetes in the rat.
We examined the contribution of prostaglandins to altered reactivity to norepinephrine in rat cremaster third order arterioles of streptozotocin (STZ) treated rats and age-matched controls. NE was applied topically to the cremaster muscle of pentobarbital (35 mg/kg) anesthetized rats before and during topical administration of indomethacin (IND: 10 micrograms/ml) four and eight weeks after i.v. injection with of 50 mg/kg STZ (STZ-4W; STZ-8W) or vehicle (C-4W; C-8W), and before and during topical administration of 5,8,11,14 eicosatetraynoic acid (ETYA; 20 micrograms/ml) in STZ-8W and C-8W. Plasma glucose was elevated significantly in STZ-treated rats. Blood pressures and resting arteriolar diameters did not differ. However, vasoconstrictor responses to NE were depressed in STZ-4W and to a greater degree in STZ-8W, IND normalized reactivity to the low doses of NE and partially restored reactivity to the higher doses. ETYA enhanced reactivity to all doses of NE to a greater extent than did IND. These data are consistent with a role for locally produced vasomodulatory arachidonic acid metabolites, including prostaglandins, in the decreased reactivity to NE in diabetic rat cremaster muscle arterioles.
Myers
T O
TO
Department of Physiology, CUNY Medical School, New York 10031, USA.
Messina
E J
EJ
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001160:Arterioles / Q000187:drug effects*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D014662:Vasoconstrictor Agents; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D013311:Streptozocin; D009638:Norepinephrine; D007213:Indomethacin