Oliver J A, Sciacca R R
J Clin Invest. 1984 Oct;74(4):1247-51. doi: 10.1172/JCI111534.
Renin is present in vascular smooth muscle cells and has been shown to coexist with angiotensins I (AI) and II (AII) in many cell types. Accordingly, we postulated that the renin-angiotensin system controls vascular tone, not by the action of circulating renal renin but rather, by the local generation of angiotensin by vascular renin. Isolated rat hindquarters were perfused in vitro with Krebs-Henseleit buffer containing 7% albumin, and flow-adjusted to obtain a perfusion pressure of approximately 90 mmHg. Infusion of 4.8 nmol X min-1 for 5 min of AII or AI markedly increased perfusion pressure. An identical dose of the synthetic tetradecaptide of renin substrate (TDCP-RS) increased pressure similarly to AI. The pressure increase evoked by TDCP-RS was markedly decreased by captopril and by two different peptides that inhibit renin. Renin activity in the perfusate, incubated with semipurified rat renin substrate, was 21 +/- 3 pg AI X ml-1 X h-1 (mean +/- SEM) at 15 min of perfusion and 47 +/- 4 pg AI X ml-1 X h-1 at 45 min (n = 9; P less than 0.01). When TDCP-RS was infused at 4.8 nmol X min-1 for 5 min in the presence of captopril, AI in the perfusate increased linearly at a rate of 16.5 pmol X min-1 for 10 min (n = 5). The results indicate that TDCP-RS constricted the vasculature by its conversion to AII and suggest that AII was generated from a two-step hydrolysis of TDCP-RS by renin and converting enzyme. The data thus suggest that the renin-angiotensin system controls vascular tone by the local generation of AII by renin and converting enzyme in the vasculature.
肾素存在于血管平滑肌细胞中，并且已证实在许多细胞类型中与血管紧张素I（AI）和II（AII）共存。因此，我们推测肾素 - 血管紧张素系统控制血管张力，不是通过循环肾素的作用，而是通过血管肾素局部生成血管紧张素。将离体大鼠后肢在体外用含7%白蛋白的Krebs - Henseleit缓冲液灌注，并调节流量以获得约90 mmHg的灌注压。以4.8 nmol·min⁻¹的速率输注AII或AI 持续5分钟，可显著增加灌注压。相同剂量的肾素底物合成十四肽（TDCP - RS）使压力升高的情况与AI相似。卡托普利和两种不同的抑制肾素的肽可显著降低TDCP - RS引起的压力升高。在灌注15分钟时，与半纯化大鼠肾素底物一起孵育的灌注液中的肾素活性为21±3 pg AI·ml⁻¹·h⁻¹（平均值±标准误），在灌注45分钟时为47±4 pg AI·ml⁻¹·h⁻¹（n = 9；P＜0.01）。当在卡托普利存在的情况下以4.8 nmol·min⁻¹的速率输注TDCP - RS 5分钟时，灌注液中的AI在10分钟内以16.5 pmol·min⁻¹的速率线性增加（n = 5）。结果表明，TDCP - RS通过转化为AII使血管收缩，并提示AII是由肾素和转换酶对TDCP - RS进行两步水解产生的。因此，这些数据表明肾素 - 血管紧张素系统通过血管中肾素和转换酶局部生成AII来控制血管张力。
