Seymour A A, Blaine E H
Arch Int Pharmacodyn Ther. 1984 Jun;269(2):304-15.
The effects of 0.01 to 40 micrograms/kg i.v. of a novel prostaglandin (PG) analog, (+)-4-[3-[3-[2-(1-hydroxycyclohexyl)ethyl]-4-oxo-2 -2-thiazolidinyl]-propyl] benzoic acid, on hemodynamic and renal functions were compared to those of the dopamine agonists SKF 82526 (0.01 to 400 micrograms/kg i.v.) and ibopamine (10-1000 micrograms/kg i.v.) in anesthetized dogs. The PG analog was the most potent renal vasodilator, maximally increasing renal blood flow (RBF) by 220 +/- 52 ml/min at 20 micrograms/kg i.v. SKF 82526 (40 micrograms/kg i.v.) and ibopamine (1000 micrograms/kg i.v.) elevated RBF by 125 +/- 18 and 74 +/- 31 ml/min, respectively. Both the PG analog and SKF 82526 significantly reduced renal vascular resistance (RVR) and were hypotensive, especially at the higher doses. In contrast, ibopamine dramatically increased mean arterial pressure (MAP) by 140 +/- 13 mm Hg at 1000 micrograms/kg i.v. Lower aortic blood flow (LAF), glomerular filtration rate (GFR), urine flow and fractional excretion rates of sodium, potassium and chloride were not altered during the 15-min period following administration of each dose of each of the compounds. The RBF and depressor responses to the PG analog and to SKF 82526 were not substantially influenced by the alpha-adrenergic antagonist, phenoxybenzamine (POB), while the pressor effect of ibopamine was reversed and dilation of the renal and hindlimb vascular beds was unmasked. The PG analog, the most potent of the three vasodilators studied, exhibited a high degree of renal specificity.
在麻醉犬中,将新型前列腺素(PG)类似物(+)-4-[3-[3-[2-(1-羟基环己基)乙基]-4-氧代-2-噻唑烷二酮基]-丙基]苯甲酸以0.01至40微克/千克静脉注射的效果,与多巴胺激动剂SKF 82526(0.01至400微克/千克静脉注射)和异波帕明(10至1000微克/千克静脉注射)对血流动力学和肾功能的影响进行了比较。PG类似物是最有效的肾血管扩张剂,静脉注射20微克/千克时最大可使肾血流量(RBF)增加220±52毫升/分钟。SKF 82526(静脉注射40微克/千克)和异波帕明(静脉注射1000微克/千克)分别使RBF增加125±18和74±31毫升/分钟。PG类似物和SKF 82526均显著降低肾血管阻力(RVR)并导致低血压,尤其是在较高剂量时。相比之下,异波帕明在静脉注射1000微克/千克时使平均动脉压(MAP)显著升高140±13毫米汞柱。在给予每种化合物的每剂后15分钟内,较低的主动脉血流量(LAF)、肾小球滤过率(GFR)、尿流量以及钠、钾和氯的分数排泄率均未改变。PG类似物和SKF 82526对RBF和降压反应基本上不受α-肾上腺素能拮抗剂酚苄明(POB)的影响,而异波帕明的升压作用被逆转,肾和后肢血管床的扩张被显现出来。PG类似物是所研究的三种血管扩张剂中最有效的,表现出高度的肾脏特异性。