Changes in cardiovascular sensitivity of alloxan-treated diabetic rats to arachidonic acid.
Arachidonic acid (AA, 0.125-2.0 mg kg-1) administered intravenously to male Wistar rats produced a dose-dependent fall in diastolic blood pressure. However AA (0.125-1.0 mg kg-1) injected into the autoperfused hindquarters via the aorta produced a dose-dependent increase in perfusion pressure. Both these responses to AA were inhibited by indomethacin (5 mg kg-1). The thromboxane A2 receptor antagonist AH23848 (5 mg kg-1, i.v.) inhibited pressor responses to AA in the autoperfused hindquarters, but potentiated depressor responses to AA (0.125-0.5 mg kg-1) in the whole animal. Alloxan-treated diabetic rats (14 days after a single s.c. injection of alloxan, 175 mg kg-1) displayed reduced sensitivity to the depressor effects of AA (1-2 mg kg-1) in the whole animal, increased sensitivity to the pressor effects of AA (0.5-1.0 mg kg-1) in the perfused hindquarters, and reduced sensitivity to the pressor effects of the thromboxane A2 mimetic U46619 (0.5-8.0 micrograms kg-1, i.a.) in the perfused hindquarters. These results suggest that AA can be predominantly converted to either pressor or depressor metabolites depending on the vasculature. In the diabetic state the ratio of the metabolites formed appears to change favouring a major pressor metabolite, which is probably thromboxane A2.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D014230:Triazoles / Q000494:pharmacology
D001095:Arachidonic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D014230:Triazoles; D016718:Arachidonic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C039993:loxtidine