Murakami M, Matsuda H, Kubota E, Wakino S, Honda M, Hayashi K, Saruta T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Kidney Int Suppl. 1997 Dec;63:S132-5.
Recent studies have provided evidence of angiotensin converting enzyme (ACE)-independent angiotensin (Ang) II formation in tissue renin-angiotensin systems. We studied the effects of Ang II generated by ACE-independent pathways on renal hemodynamics. We used a synthetic peptide, [Pro11, D-Ala12]-Ang I (S), which yields Ang II by chymase, but not by ACE. Infusion of Ang I into a renal artery caused a decrease in renal blood flow, and reciprocally an increase in mean arterial pressure. Infusion of S (1 nmol/kg) caused a decrease in renal blood flow (-20%), but a larger dose was needed to increase mean arterial pressure. Studies with an intravital needle-probe CCD camera revealed that the Ang I infusion induced dose-dependent vasoconstriction of afferent and efferent arterioles (49% and 54%, respectively at 1 nmol/kg). In contrast, infusion of S elicited only 30% constriction of these vessels at a dose of 1 nmol/kg and induced no further constriction at higher doses, indicating that different segments of renal vessels responded in different fashions to Ang II formed via ACE-independent pathways. These vasoconstrictions were abolished by an angiotensin II receptor (AT-1) antagonist. Enzymatic assays using reverse-phase HPLC revealed that the ACE-dependent pathway was predominant in the rena1 cortex (approximately 80%). We also determined Ang II concentrations in renal cortex specimens obtained by needle biopsy. Intrarenal S infusion (10 nmol/kg) increased plasma and renal Ang II concentrations to 160% and 710% of the respective baseline levels. This study provides in vivo evidence of ACE-independent Ang II formation in renal tissue and suggests that this locally-formed Ang II influences the renal circulation in a paracrine fashion.
近期研究已提供证据表明，在组织肾素 - 血管紧张素系统中存在不依赖血管紧张素转换酶（ACE）的血管紧张素（Ang）II生成。我们研究了由不依赖ACE的途径产生的Ang II对肾血流动力学的影响。我们使用了一种合成肽，[Pro11，D - Ala12] - Ang I（S），其通过糜酶产生Ang II，但不通过ACE产生。将Ang I注入肾动脉会导致肾血流量减少，反之平均动脉压升高。注入S（1 nmol/kg）会导致肾血流量减少（-20%），但需要更大剂量才能升高平均动脉压。使用活体针探头CCD相机进行的研究表明，注入Ang I会引起入球小动脉和出球小动脉剂量依赖性血管收缩（在1 nmol/kg时分别为49%和54%）。相比之下，注入S在1 nmol/kg剂量时仅引起这些血管30%的收缩，且在更高剂量时未引起进一步收缩，这表明肾血管的不同节段对通过不依赖ACE的途径形成的Ang II有不同的反应方式。这些血管收缩被血管紧张素II受体（AT - 1）拮抗剂消除。使用反相高效液相色谱进行的酶活性测定表明，依赖ACE的途径在肾皮质中占主导地位（约80%）。我们还测定了通过针吸活检获得的肾皮质标本中的Ang II浓度。肾内注入S（10 nmol/kg）使血浆和肾Ang II浓度分别升高至各自基线水平的160%和710%。本研究提供了肾组织中存在不依赖ACE的Ang II生成的体内证据，并表明这种局部形成的Ang II以旁分泌方式影响肾循环。
