Levens N R, Freedlender A E, Peach M J, Carey R M
Endocrinology. 1983 Jan;112(1):43-9. doi: 10.1210/endo-112-1-43.
The purpose of this study was to determine if endogenous angiotensin II affects renal function in conscious dogs after sodium restriction. Intrarenal infusion of the angiotensin receptor antagonist saralasin at doses between 0.13 and 2.5 micrograms/kg X min rapidly attenuated pressor responses produced by systemic injections of angiotensin I over a 90-min period. In contrast, intrarenal infusion of the peptide antagonist at 0.07 microgram/ kg X min did not alter the pressor response to injected angiotensin I. Infusion of angiotensin II into the kidney at 0.1 microgram/min reduced urine output by 50% and was totally inhibited by simultaneous infusion of 0.07 micrograms/kg X min saralasin. Intrarenal infusion of saralasin at 0.07 micrograms/kg X min into sodium-restricted conscious dogs increased effective renal plasma flow, glomerular filtration rate, and sodium, potassium and water excretion, whereas urine osmolarity and free water formation were unchanged. These data demonstrate that saralasin can be effectively confined to the renal mass after intrarenal infusion at a dose capable of inhibiting angiotensin action and that endogenous angiotensin plays an important role in maintaining renal function after sodium restriction.
本研究的目的是确定内源性血管紧张素II在钠限制后是否影响清醒犬的肾功能。肾内输注剂量为0.13至2.5微克/千克×分钟的血管紧张素受体拮抗剂沙拉新,在90分钟内迅速减弱了全身注射血管紧张素I所产生的升压反应。相比之下,肾内以0.07微克/千克×分钟的剂量输注该肽拮抗剂,并未改变对注射血管紧张素I的升压反应。以0.1微克/分钟的速度向肾脏输注血管紧张素II可使尿量减少50%,并被同时输注0.07微克/千克×分钟的沙拉新完全抑制。向钠限制的清醒犬肾内输注0.07微克/千克×分钟的沙拉新,可增加有效肾血浆流量、肾小球滤过率以及钠、钾和水的排泄,而尿渗透压和自由水生成则未改变。这些数据表明,肾内输注能够抑制血管紧张素作用的剂量的沙拉新后,其可有效局限于肾脏,并且内源性血管紧张素在钠限制后维持肾功能方面发挥重要作用。