Frechilla D, Bernedo E, Castiella E, Lasheras B, Cenarruzabeitia E, Monge A, Aldana I, Alvarez T, Losa M J, Font M
Department of Pharmacology, Universidad de Navarra, Pamplona, Spain.
Eur J Pharmacol. 1992 Sep 4;219(3):409-14. doi: 10.1016/0014-2999(92)90482-j.
The hypotensive and antihypertensive activities of a A-80b, a newly synthesized pyridazino[4,5-b]indole derivate were investigated in anaesthetized rats. In vitro studies were also done to examine the possible mechanism of its vasodilator action. A 80b (3-15 mg/kg i.p.) showed potent and long-lasting antihypertensive activity in spontaneous hypertensive rats. In normotensive rats, A-80b (7.5-30 mg/kg i.p.) also lowered blood pressure but less than in hypertensive rats. The decrease in diastolic pressure was greater than the decrease in systolic pressure and cardiac frequency was not modified significantly. Contractile responses induced in isolated rat thoracic aorta by K+ and noradrenaline were inhibited by A-80b. In K(+)-depolarized rat aorta, A-80b showed dose-dependent inhibition of the Ca(2+)-induced contraction. Also, A-80b inhibited spontaneous contractions of rat portal vein. The vasodilator action seemed to be endothelium-independent. These results suggest that A-80b is a new chemical entity which exerts a hypotensive and antihypertensive effect, possibly attributable to vasodilator activity via interference with Ca2+ influx and probably Ca2+ mobilization from intracellular stores.
对新合成的哒嗪并[4,5 - b]吲哚衍生物A - 80b在麻醉大鼠中的降压及抗高血压活性进行了研究。还进行了体外研究以考察其血管舒张作用的可能机制。A - 80b（腹腔注射3 - 15毫克/千克）在自发性高血压大鼠中显示出强效且持久的抗高血压活性。在正常血压大鼠中，A - 80b（腹腔注射7.5 - 30毫克/千克）也能降低血压，但降幅小于高血压大鼠。舒张压的下降幅度大于收缩压的下降幅度，且心率无明显改变。A - 80b抑制了钾离子（K⁺）和去甲肾上腺素在离体大鼠胸主动脉中诱导的收缩反应。在钾离子去极化的大鼠主动脉中，A - 80b对钙离子（Ca²⁺）诱导的收缩呈剂量依赖性抑制。此外，A - 80b抑制大鼠门静脉的自发收缩。其血管舒张作用似乎不依赖于内皮细胞。这些结果表明，A - 80b是一种新的化学实体，具有降压和抗高血压作用，可能归因于通过干扰钙离子内流以及可能从细胞内储存库动员钙离子而产生的血管舒张活性。
