1-Benzylimidazole, a thromboxane synthetase inhibitor acutely lowers blood pressure mainly by alpha-adrenoceptor blockade in spontaneously hypertensive rats (SHR).
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.
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
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