{'fraction_non_alphanumeric': 0.03910614525139665, 'fraction_numerical': 0.017877094972067038, 'mean_word_length': 5.071186440677966, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Effects of BQ‐485, a Selective ETA Antagonist, on Endothelin‐Mediated Vasomotion in Rat Coronary Vascular Beds

Summary: The effects of BQ-485, a selective endothelin (ET)-A receptor antagonist, on the vasomotion induced by a low dose of ET were investigated. In the isolated rat heart perfused with Krebs-Henseleit solution at a constant flow, intracoronary bolus injection of ET-1 or ET-3 (10 pmol) elicited a rapid transient decrease, followed by a slight sustained increase, in the coronary perfusion pressure (CPP). The decrease in CPP induced by ET-1 was similar in magnitude to (—30%) but shorter in duration than that induced by ET-3. Pretreatment of the heart with saponin (30 μg/ml) to denude the coronary endothelium abolished the decrease and markedly enhanced the increase in CPP induced by ETs, indicating that the va-sorelaxing action of ETs is endothelium-dependent. The selective ETA receptor antagonist BQ-485 (1 μM) significantly prolonged the duration of the ET-1-induced decrease in CPP, made the vasodilatation by ET-1 indistinguishable from that by ET-3, and eliminated the subsequent increase in CPP. In the saponin-treated heart, BQ-485 also eliminated the ET-1-mediated increase in CPP. These findings suggest that, in rat coronary vascular beds, a low dose of ET-1 elicits vasoconstriction and endothelium-dependent vasodilatation through the ETA receptor on the vascular smooth muscle and presumably the ETB receptor on the endothelium, respectively. Furthermore, it is expected that selective ETA receptor antagonists, including BQ-485, may be able to protect the heart against ET-1-induced coronary spasm in situations, such as hyperlipidemia or atherosclerosis, in which the release and/ or function of endothelium-derived vasorelaxing substances is impaired.