Premium
Changes in cardiovascular sensitivity of alloxan‐treated diabetic rats to arachidonic acid
Author(s) -
Boura A.L.A.,
Hodgson W.C.,
King R.G.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb11163.x
Subject(s) - endocrinology , medicine , thromboxane a2 , arachidonic acid , thromboxane b2 , thromboxane , metabolite , chemistry , alloxan , perfusion , blood pressure , diabetes mellitus , receptor , platelet , biochemistry , enzyme
1 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 ). 2 The thromboxane A 2 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. 3 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 A 2 mimetic U46619 (0.5–8.0 μg kg −1 , i.a.) in the perfused hindquarters. 4 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 A 2 .