[The release of thromboxane A2 and prostacyclin due to vasoactive agents in hypercholesterolemic rabbits].
The production of Thromboxane A2 (TXA2) and Prostacyclin (PGI2) in hypercholesterolemic state is considered to be different from that in normal state. The purpose of this study was to investigate the effect of vasoactive agents on the release of TXA2 and PGI2 in hypercholesterolemic rabbits (HCR). Hypercholesterolemia was induced in rabbits by feeding pellet food containing 1% cholesterol for 3 months. After blood sampling and blood pressure (BP) measurement in basal state, vasoactive agents such as ergonovine 2.0 mg/kg, norepinephrine 10.0 micrograms/kg and angiotensin II 0.5 micrograms/kg were administered intravenously to rabbits under the infusion of saline or vasodilators such as nitroglycerin 40 micrograms/kg/min and verapamil 20 micrograms/kg/min to suppress the increase in systolic BP (SBP) due to vasoactive agents. BP response was recorded, and blood was collected after BP returned to pre-injection level of vasoactive agents. TXA2 and PGI2 were measured as TXB2 and 6-keto-PGF1 alpha respectively by radioimmunoassay. Administration of the vasoactive agents increased the plasma level of both TXB2 and 6-keto-PGF1 alpha in normal control rabbits (NCR), whereas in HCR only TXB2 was markedly increased. The increase in TXB2 was suppressed by inhibiting the rise in SBP by vasodilators both in NCR and HCR. Neither TXB2 synthesis nor phospholipase A2 activity in platelets was affected by the vasoactive agents in vitro. These results suggest that the increase in SBP due to vasoactive agents affects on TXB2 release in vivo and we concluded that the release of TXB2 by BP response was greater in HCR than in NCR.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D011464:Epoprostenol / Q000378:metabolism*; D004874:Ergonovine / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D013928:Thromboxane A2 / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D000804:Angiotensin II; D013928:Thromboxane A2; D014700:Verapamil; D011464:Epoprostenol; D005996:Nitroglycerin; D004874:Ergonovine; D009638:Norepinephrine