Contractile responses of mammalian cerebral arteries to 15-hydroperoxyarachidonic acid vary in the presence of fusaric acid and verapamil.

The effects of fusaric acid and verapamil on 15-hydroperoxyarachidonic acid (15-HPAA)-induced cerebral arterial contraction were examined. Addition to the tissue bath of 15-HPAA in concentrations ranging from 1 X 10(-7) to 3 X 10(-5) M caused a dose-dependent contraction in canine basilar, middle cerebral, posterior cerebral and human basilar or middle cerebral arteries. Fusaric acid and verapamil antagonized the 15-HPAA-induced contraction of these cerebral arteries by different mechanisms, in a dose-dependent manner. In the presence of 1 X 10(-3) M fusaric acid, the dose-response curves of cerebral arteries for 15-HPAA were antagonized in a noncompetitive manner. However, the responses to 15-HPAA were restored completely after removal of fusaric acid from the bathing solution. Fusaric acid did not antagonize the CaCl2-induced contraction. The concentration of verapamil which antagonized the 15-HPAA-induced contraction was a good fit to the concentration of this antagonist which antagonized the CaCl2-induced contraction. These findings indicate that the antagonism seen with fusaric acid manifests as a block of the sites specific for 15-HPAA and that the antagonistic actions of verapamil on 15-HPAA may be produced by the inhibition of calcium influx.