Effect of the thromboxane A2 mimetic U 46619 on pial arterioles of rabbits and rats.
Our previous experiments have shown that thromboxane A2 is a strong contractor of cerebral arterial smooth muscle strips. The objective of these experiments was to determine if U 46619, a stable thromboxane A2 mimetic, affects the cerebral microcirculation in vivo. Pial arteriole diameter in rabbits and rats was measured with a microscope using the closed cranial window technique. Topical application of 10(-11) to 10(-6) M U 46619 induced dose-dependent arteriole vasoconstriction in both species. In rabbits and rats the maximum vasoconstriction was 9.7 +/- 1.3% (mean +/- SEM) and 14.0 +/- 0.5%, respectively. In rats, 10(-7) and 10(-6) M U 46619 induced intravascular platelet aggregation accompanied by a further decrease in diameter and transient occlusion of the arterioles and venules. U 46619 had no significant effect on rabbit pial arterioles that were predilated by hypercapnia or hypercapnia plus hypoxia. Our data suggest that in animals with a normal vasculature, thromboxane A2 may be a moderate constrictor of cerebral arterioles and that this constrictor effect is prevented by hypercapnia and hypoxia.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D001160:Arterioles / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006935:Hypercapnia / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D010841:Pia Mater / Q000098:blood supply*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013928:Thromboxane A2 / Q000494:pharmacology*; D014661:Vasoconstriction
D004338:Drug Combinations; D011450:Prostaglandin Endoperoxides, Synthetic; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007213:Indomethacin