Lehoux S, Sirois M G, Sirois P, Plante G E
Department of Medicine, University of Sherbrooke, Québec, Canada.
J Pharmacol Exp Ther. 1994 Jun;269(3):1094-9.
Diuretics are widely used antihypertensive agents, and although their renal actions have been well characterized, the extent of their vascular effects remains to be defined. Because hypertension is associated with numerous vascular complications whose incidences are not always lowered once blood pressure is regulated, this study was undertaken to evaluate the effects of five selected diuretics on capillary permeability to see if they could contribute in some way to these vascular abnormalities. Extravasation of Evans blue dye (EB: 20 mg/kg) injected in the caudal vein of male Wistar rats was used to assess capillary permeability to albumin. Indapamide (0.04 mg/kg), cicletanine (2.0 mg/kg), amiloride (0.3 mg/kg), hydrochlorothiazide (0.5 mg/kg) and furosemide (0.5 mg/kg) were administered by acute i.v. injection or by 10-day "chronic" gavage. EB extravasation was increased in the upper bronchi, lung parenchyma and kidney after acute administration of indapamide (54, 41 and 31%, respectively) and hydrochlorothiazide (45, 41 and 19%, respectively), and increased in all tissues but the duodenum (upper bronchi, lung parenchyma, heart, liver, kidney and muscle; 57-118%) after furosemide. In contrast, capillary permeability was reduced after acute cicletanine in the heart (31%), duodenum (49%) and muscle (58%) and after amiloride in the heart (25%) and muscle (63%). Pretreatment with indomethacin abolished most changes in EB extravasation induced by acute injection of the diuretics. After 10-day gavage, however, changes in capillary permeability were null after amiloride or hydrochlorothiazide treatment, attenuated after cicletanine or furosemide or even reversed after indapamide. Arterial pressure was not affected by diuretic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
利尿剂是广泛使用的抗高血压药物，尽管其对肾脏的作用已得到充分描述，但其对血管的影响程度仍有待确定。由于高血压与许多血管并发症相关，而这些并发症的发生率在血压得到控制后并非总能降低，因此本研究旨在评估五种选定利尿剂对毛细血管通透性的影响，以确定它们是否能以某种方式导致这些血管异常。通过注射伊文思蓝染料（EB：20mg/kg）至雄性Wistar大鼠尾静脉外渗情况来评估毛细血管对白蛋白的通透性。吲达帕胺（0.04mg/kg）、环戊噻嗪（2.0mg/kg）、阿米洛利（0.3mg/kg）、氢氯噻嗪（0.5mg/kg）和呋塞米（0.5mg/kg）通过急性静脉注射或10天“慢性”灌胃给药。急性给予吲达帕胺（分别为54%、41%和31%）和氢氯噻嗪（分别为45%、41%和19%）后，上支气管、肺实质和肾脏的EB外渗增加；呋塞米给药后，除十二指肠外的所有组织（上支气管、肺实质、心脏、肝脏、肾脏和肌肉；57 - 118%）的EB外渗增加。相比之下，急性给予环戊噻嗪后，心脏（31%）、十二指肠（49%）和肌肉（58%）的毛细血管通透性降低；阿米洛利给药后，心脏（25%）和肌肉（63%）的毛细血管通透性降低。用吲哚美辛预处理可消除急性注射利尿剂引起的大多数EB外渗变化。然而，10天灌胃后，阿米洛利或氢氯噻嗪治疗后毛细血管通透性无变化，环戊噻嗪或呋塞米治疗后变化减弱，吲达帕胺治疗后甚至逆转。利尿剂治疗对动脉血压无影响。（摘要截选至250字）
