Unwin R J, Mathias C J, Peart W S, Frankel H L
Clin Exp Hypertens A. 1986;8(6):919-39. doi: 10.3109/10641968609044078.
To determine the relative contributions of direct angiotensin-II-like myotropism and sympathetic nerve stimulation to the partial agonist effect of saralasin, the renal vascular responses to i.v. saralasin (5, 10, 20 micrograms/kg/min) were assessed in normal conscious rabbits before and after sympatholytic treatment with guanethidine (24 mg/kg/day for 9 days) and in 6 chronic tetraplegic patients (0.5, 1, 5 micrograms/kg/min) before and after alpha-adrenoreceptor blockade with i.v. thymoxamine (1 mg/kg/h). In rabbits saralasin reduced effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), and increased renal vascular resistance (RVR) without affecting mean arterial blood pressure (BP). Responses were similar in both groups, but recovery following saralasin was more prolonged after treatment with guanethidine. When 0.1 microgram/kg/min (one fiftieth of the smallest i.v. dose) was infused just proximal to the renal arteries in 4 conscious rabbits (chronically cannulated), renal perfusion fell and RVR increased. In tetraplegics saralasin produced a transient rise in BP and variable increase in RVR; neither response being altered by thymoxamine. These results suggest that saralasin-induced renal vasoconstriction is independent of central and peripheral sympathetic activation, and is probably due to an intrinsic angiotensin-II-like myotropic action.
为了确定直接的血管紧张素II样肌性作用和交感神经刺激对沙拉新部分激动剂效应的相对贡献，我们评估了正常清醒家兔在用胍乙啶（24mg/kg/天，共9天）进行交感神经阻滞治疗前后静脉注射沙拉新（5、10、20微克/千克/分钟）时的肾血管反应，以及6例慢性四肢瘫痪患者在静脉注射百里胺（1mg/kg/小时）进行α-肾上腺素能受体阻滞前后静脉注射沙拉新（0.5、1、5微克/千克/分钟）时的肾血管反应。在家兔中，沙拉新降低了有效肾血浆流量（ERPF）和肾小球滤过率（GFR），并增加了肾血管阻力（RVR），而不影响平均动脉血压（BP）。两组的反应相似，但在用胍乙啶治疗后，沙拉新作用后的恢复时间延长。当向4只清醒家兔（长期插管）的肾动脉近端仅输注0.1微克/千克/分钟（静脉最小剂量的五十分之一）时，肾灌注下降，RVR增加。在四肢瘫痪患者中，沙拉新使血压短暂升高，RVR有不同程度的增加；两种反应均未被百里胺改变。这些结果表明，沙拉新诱导的肾血管收缩独立于中枢和外周交感神经激活，可能是由于内在的血管紧张素II样肌性作用。
