title: The hypertensive response to vasopressor agents stimulates the release of thromboxane A2 in hypercholesterolaemic rabbits.
abstract: The production of thromboxane A2 (TXA2) and prostacyclin (PGI2) is altered in hypercholesterolaemia. The purpose of this study was to investigate the effect of an acute rise in arterial pressure produced by pressor agents on the release of TXA2 and PGI2 in hypercholesterolaemic rabbits. Hypercholesterolaemia was induced in rabbits by feeding pellet food containing 1% cholesterol for 3 months. Administration of pressor agents (ergonovine 0.5-2.0 mg.kg-1, noradrenaline 5.0-20.0 micrograms.kg-1 and angiotensin-II 0.5-2.0 micrograms.kg-1) increased arterial pressure dose dependently, accompanied by a pressure dependent increase in the plasma concentrations of both TXB2 and 6-keto-PGF1 alpha (stable metabolites of TXA2 and PGI2) in control rabbits, but only of TXB2 in hypercholesterolaemic rabbits. In control rabbits the maximum increase in TXB2 was 51% with ergonovine, 73% with noradrenaline, and 51% with angiotensin-II; and the maximum increase in 6-keto-PGF1 alpha was 48% with ergonovine, 76% with noradrenaline, and 198% with angiotensin-II. In hypercholesterolaemic rabbits the maximum increase in TXB2 was 130% with ergonovine, 144% with noradrenaline, and 128% with angiotensin-II. The pressor induced increase in TXB2 was suppressed when the increase in arterial pressure was counteracted by the concomitant administration of vasodilators (glyceryl trinitrate 40 micrograms.kg-1.min-1 and verapamil 20 micrograms.kg-1.min-1) in both control and hypercholesterolaemic rabbits. Neither TXB2 biosynthesis nor phospholipase A2 activity in platelets was affected by ergonovine, noradrenaline or angiotensin-II in vitro. These results suggested that the acute rise in arterial pressure caused by these pressor agents increased TXA2 release in vivo and that the increase was greater in hypercholesterolaemic than in control rabbits.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000096:biosynthesis*; D004874:Ergonovine / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000097:blood*; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000097:blood; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000804:Angiotensin II; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D014700:Verapamil; D011464:Epoprostenol; D005996:Nitroglycerin; D004874:Ergonovine; D009638:Norepinephrine