吡咯他尼的血管作用。在几种动物模型中的肾外作用研究。

Vascular effects of piretanide. Studies on extrarenal action in several animal models.

作者信息

Klaus E, Alpermann H G, Caspritz G, Linz W, Schölkens B

出版信息

Arzneimittelforschung. 1983;33(9):1273-6.

Abstract

4-Phenoxy-3-(1-pyrrolidinyl)-5-sulfamoyl benzoic acid (piretanide, Arelix) was studied for its vasoactive effects in several experimental models. In rat and rabbit thoracic aorta strips, piretanide dose-dependently attenuated contractions induced by norepinephrine (noradrenaline). When contractions were induced by KCl no concentration response curve could be established. Piretanide inhibited the vasoconstrictor response to norepinephrine and to KCl in the rat mesenteric vascular bed. IC50's of 0.5 mmol/l and 4.9 mmol/l, resp., were calculated. In bovine coronary artery strips piretanide caused a marked relaxation. The vasoconstrictor response to PGE2 in piretanide superfused preparations was attenuated in a concentration related manner. Infusion of piretanide (1 mg X ml-1 X min-1) in the isolated guinea pig heart produced a reversible increase of coronary flow. In both normotensive and spontaneously hypertensive bilaterally nephrectomized pithed rats piretanide caused a significant reduction of diastolic blood pressure. The results contribute to the understanding of the antihypertensive effect of piretanide.

摘要

研究了4-苯氧基-3-(1-吡咯烷基)-5-氨磺酰苯甲酸（吡咯他尼，阿瑞利克）在多种实验模型中的血管活性作用。在大鼠和兔胸主动脉条中，吡咯他尼剂量依赖性地减弱去甲肾上腺素（去甲肾上腺素）诱导的收缩。当由氯化钾诱导收缩时，无法建立浓度反应曲线。吡咯他尼抑制大鼠肠系膜血管床对去甲肾上腺素和氯化钾的血管收缩反应。分别计算出IC50为0.5 mmol/l和4.9 mmol/l。在牛冠状动脉条中，吡咯他尼引起明显的舒张。在吡咯他尼灌流的制剂中，对前列腺素E2的血管收缩反应以浓度相关的方式减弱。在离体豚鼠心脏中输注吡咯他尼（1 mg·ml-1·min-1）导致冠状动脉流量可逆性增加。在正常血压和自发性高血压双侧肾切除的脊髓麻醉大鼠中，吡咯他尼均导致舒张压显著降低。这些结果有助于理解吡咯他尼的降压作用。