title: 1-Benzylimidazole, a thromboxane synthetase inhibitor acutely lowers blood pressure mainly by alpha-adrenoceptor blockade in spontaneously hypertensive rats (SHR).
abstract: Selective inhibitors of thromboxane (TX) formation have potential utility in the treatment of hypertension, atherosclerosis, thrombosis, myocardial ischemia, cancer metastasis, etc. This class of compounds not only removes TX, a potent vasoconstrictor and inducer of platelet aggregation, but may also enhance the production of a potent vasodilator and inhibitor of platelet aggregation, viz., prostacyclin (epoprostenol, PGI2). The specific thromboxane synthetase (TXS) inhibitor 1-benzylimidazole (1-BI) demonstrated a weak and OKY-1581 (OKY) a potent inhibition of TX formation in SHR-derived platelets in vitro. The acute antihypertensive effects produced by 1-BI were marked while those of OKY were less significant in SHR. 1-BI and OKY did not demonstrate an inhibition of PGI2 formation in SHR-derived aortic rings in vitro. Indomethacin (I), which inhibits the formation of both TX and PGI2, was not antihypertensive and did not antagonize the blood pressure lowering effects of 1-BI in the present studies. Oral and intravenous dosing with 1-BI, unlike OKY, produced epinephrine reversal in SHR, indicating the blockade of alpha-adrenoceptors. In conclusion, the acute antihypertensive effects of 1-BI in SHR result mainly from alpha-adrenoceptor blockade, not inhibition of TXS activity.
mesh_terms: D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D011464:Epoprostenol / Q000096:biosynthesis; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008689:Methacrylates / Q000494:pharmacology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D051381:Rats; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013931:Thromboxanes / Q000096:biosynthesis
chemical_list: D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D008689:Methacrylates; D013931:Thromboxanes; C017062:1-benzylimidazole; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D011464:Epoprostenol; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase