Oates H F, Stokes G S, Storey B G, Glover R G, Snow B F
J Exp Med. 1974 Feb 1;139(2):239-48. doi: 10.1084/jem.139.2.239.
Rats, actively immunized against angiotensin I (AI) and angiotensin II (AII), were subjected to unilateral renal artery constriction to determine whether the resulting hypertension, which may still ensue in the animal immunized against AII, could be prevented by such combined immunity. Sustained immunity to both AI and AII neither changed preoperative blood pressures of the rats from those of control mock-immunized rats nor altered the incidence or severity of renal dip hypertension. Vascular hyperresponsiveness to small quantities of free angiotensin could not be invoked to explain the hypertension, for there was no significant difference between mock-immunized hypertensive animals, and those remaining normotensive, regarding pressor sensitivity to intravenous AI, AII, renin, and norepinephrine. (AI + AII)-immunized hypertensive rats required AI doses averaging 260 times greater than nonimmune hypertensives to elicit equipressor responses, and were refractory to renin, but not to norepinephrine. Thus, while previous studies have not excluded direct participation of endogenous AI in renal clip hypertension in rats, evidence from our experiments makes it extremely difficult to sustain any pressor function therein for circulating AI or AII. Our results also preclude involvement of AII produced from circulating AI by conversion within arteriolar walls, close to receptor sites, since AI immunity would block this mechanism of action.
用血管紧张素I(AI)和血管紧张素II(AII)对大鼠进行主动免疫后,对其进行单侧肾动脉狭窄手术,以确定在针对AII免疫的动物中可能仍然会出现的高血压是否可以通过这种联合免疫来预防。对AI和AII的持续免疫既没有使大鼠的术前血压与对照假免疫大鼠的血压有所不同,也没有改变肾夹高血压的发生率或严重程度。不能用对少量游离血管紧张素的血管高反应性来解释高血压,因为在假免疫的高血压动物和保持血压正常的动物之间,对静脉注射AI、AII、肾素和去甲肾上腺素的升压敏感性没有显著差异。(AI + AII)免疫的高血压大鼠引发等压反应所需的AI剂量平均比非免疫性高血压大鼠大260倍,并且对肾素不敏感,但对去甲肾上腺素敏感。因此,虽然先前的研究没有排除内源性AI直接参与大鼠肾夹高血压,但我们实验的证据使得很难维持循环中的AI或AII在其中的任何升压功能。我们的结果也排除了在靠近受体部位的小动脉壁内通过循环AI转化产生的AII的参与,因为AI免疫会阻断这种作用机制。