title: Sensitivity changes of the perfused hindquarters' vasculature in rats with alloxan-induced diabetes mellitus.
abstract: 1. Arachidonic acid (AA, 0.125-1.0 mg/kg) injected via the aorta into the autoperfused hindquarters caused dose-dependent increases in perfusion pressure. This effect was reduced after intravenous administration of the thromboxane receptor antagonist AH23848 (5 mg/kg) or indomethacin (5 mg/kg). 2. Responses to AA (0.125-1.0 mg/kg) were reduced markedly in the Krebs-perfused hindquarters when compared with those occurring in the blood-perfused preparation. 3. Doses of guanethidine (1 mg/kg) and pentacynium (1 mg/kg) blocking pressor responses to intravenous administration of the ganglion stimulants McN-A-343 and DMPP, respectively, did not affect responses to AA. 4. Constrictor responses to AA (0.5-1.0 mg/kg) in blood-perfused hindquarters were increased in 14 day alloxan-diabetic rats but those to the thromboxane A2-mimetic U46619 (0.5-8.0 micrograms/kg, i.a.) were reduced when compared with non-diabetic controls. 5. In 14 day alloxan-diabetic rats vasoconstrictor responses to noradrenaline and methoxamine were potentiated but those to 5-hydroxytryptamine were reduced compared with non-diabetic animals. 6. It is concluded that AA causes constriction in the blood-perfused hindquarters by release of a product of cyclo-oxygenase acting on thromboxane A2-receptors. A constituent of blood, perhaps the platelet, appears necessary for this effect. Conversion of AA to the constrictor metabolite is augmented during experimentally induced diabetes.
authors: Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors: A L
authors: AL
authors: Boura
authors: W C
authors: WC
authors: Hodgson
authors: R G
authors: RG
authors: King
mesh_terms: D000496:Alloxan; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006614:Hindlimb / Q000187:drug effects; D010477:Perfusion; D011312:Pressure; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001095:Arachidonic Acids; D000496:Alloxan