Hilgers K F, Fischli W, Veelken R, Mann J F
Department of Medicine, University of Erlangen, Germany.
Hypertension. 1994 Jun;23(6 Pt 2):861-4. doi: 10.1161/01.hyp.23.6.861.
Angiotensin I and II are generated by the vascular wall. Whether this generation depends on renin or on other enzymes is debated. We tested the hypothesis that remikiren, a highly specific inhibitor of human and guinea pig renin, may inhibit the vascular renin-angiotensin system. Isolated hindquarters from guinea pigs were perfused with an artificial medium, and angiotensin I and II release was measured by high-performance liquid chromatography and radioimmunoassay. Guinea pig hindquarters released angiotensin I (23.8 +/- 5.6 fmol/30 min; n = 13) and angiotensin II (95.2 +/- 19 fmol/30 min; n = 13) spontaneously. Inhibition of the angiotensin I-converting enzyme by captopril (10 nmol/mL) suppressed angiotensin II by 85% and increased angiotensin I by 352% (n = 5, P < .05). Infusion of remikiren (1.6 nmol/mL) in addition to captopril decreased angiotensin I release by 68% (P < .05 versus captopril alone, n = 5 each). We conclude that renin generates angiotensin I in an isolated guinea pig resistance vessel bed. Our study demonstrates that renin rather than nonrenin enzymes is responsible for the major part of vascular angiotensin formation.
血管紧张素I和II由血管壁产生。这种产生是依赖肾素还是其他酶存在争议。我们检验了一种假说，即瑞米吉仑（一种人和豚鼠肾素的高度特异性抑制剂）可能抑制血管肾素-血管紧张素系统。用人工培养基灌注豚鼠分离的后肢，通过高效液相色谱法和放射免疫分析法测量血管紧张素I和II的释放。豚鼠后肢可自发释放血管紧张素I（23.8±5.6 fmol/30分钟；n = 13）和血管紧张素II（95.2±19 fmol/30分钟；n = 13）。卡托普利（10 nmol/mL）抑制血管紧张素I转换酶后，血管紧张素II减少85%，血管紧张素I增加352%（n = 5，P <.05）。在卡托普利基础上输注瑞米吉仑（1.6 nmol/mL）使血管紧张素I释放减少68%（与单独使用卡托普利相比，P <.05，每组n = 5）。我们得出结论，肾素在分离的豚鼠阻力血管床中产生血管紧张素I。我们的研究表明，肾素而非非肾素酶是血管紧张素形成的主要原因。
