Takase H, Dohi Y, Kojima M, Sato K
Second Department of Internal Medicine, Nagoya City University Hospital, Japan.
J Cardiovasc Pharmacol. 1994 Feb;23(2):326-30.
Vasodilator responses to adenosine and acetylcholine (ACh) were studied in ring preparations of mesenteric resistance arteries of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Adenosine (10(-7)-3 x 10(-4) M) caused relaxations in rings with endothelium. The relaxation was more pronounced in WKY than in SHR. Removal of the endothelium in WKY, but not in SHR, reduced the relaxation. In rings without endothelium, the relaxation was identical in the two strains. In WKY, the cyclooxygenase inhibitor meclofenamic acid attenuated the relaxation to adenosine in rings with endothelium but not in rings without endothelium. With meclofenamic acid, the relaxation was identical in WKY arteries with and without endothelium. ACh (10(-9)-10(-4) M) evoked endothelium-dependent relaxations in WKY. In contrast, in SHR the muscarinic agonist evoked contractions at higher concentrations (10(-6)-10(-4) M), whereas lower concentrations of ACh caused relaxations similar to those observed in WKY. The contraction in SHR was completely inhibited by meclofenamic acid, and with meclofenamic acid the relaxation to ACh was identical in WKY and SHR. Thus, adenosine evokes endothelium-dependent (through release of cyclooxygenase product) and endothelium-independent relaxations and ACh evokes endothelium-dependent relaxations in rat mesenteric resistance arteries. In SHR, the endothelium-dependent responses to the agonists are altered owing to the changes in the endothelial cyclooxygenase pathway.
在Wistar-Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）的肠系膜阻力动脉环标本中研究了血管舒张剂对腺苷和乙酰胆碱（ACh）的反应。腺苷（10⁻⁷ - 3×10⁻⁴ M）可使有内皮的血管环舒张。WKY中的舒张比SHR中更明显。去除WKY的内皮，但不包括SHR的内皮，会降低舒张反应。在无内皮的血管环中，两种品系的舒张反应相同。在WKY中，环氧化酶抑制剂甲氯芬那酸减弱了有内皮血管环对腺苷的舒张反应，但对无内皮血管环没有影响。使用甲氯芬那酸后，有内皮和无内皮的WKY动脉的舒张反应相同。ACh（10⁻⁹ - 10⁻⁴ M）在WKY中引起内皮依赖性舒张。相反，在SHR中，毒蕈碱激动剂在较高浓度（10⁻⁶ - 10⁻⁴ M）时引起收缩，而较低浓度的ACh引起与WKY中观察到的相似的舒张。SHR中的收缩被甲氯芬那酸完全抑制，使用甲氯芬那酸后，WKY和SHR对ACh的舒张反应相同。因此，腺苷在大鼠肠系膜阻力动脉中引起内皮依赖性（通过释放环氧化酶产物）和非内皮依赖性舒张，而ACh引起内皮依赖性舒张。在SHR中，由于内皮环氧化酶途径的变化，对激动剂的内皮依赖性反应发生改变。
