Gao X P, Anding P, Robbins R A, Rennard S I, Rubinstein I
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-4575.
Am J Physiol. 1994 Jan;266(1 Pt 2):H93-8. doi: 10.1152/ajpheart.1994.266.1.H93.
The purpose of this study was to investigate whether angiotensin-converting enzyme (ACE; EC 3.4.15.1) and neutral endopeptidase (NEP; EC 3.4.24.11), two membrane-bound metalloenzymes that are widely distributed in the peripheral microcirculation and degrade kinins very effectively, modulate bradykinin-induced arteriolar dilation in vivo. Using intravital microscopy, we measured diameter of second-order arterioles in the hamster cheek pouch during suffusion of bradykinin (0.1-10.0 microM) before and after topical application of captopril (10.0 microM) and phosphoramidon (10.0 nM). We found that each inhibitor significantly potentiated bradykinin-induced increase in arteriolar diameter (P < 0.05). Suffusion of other proteinase inhibitors (excluding ACE and NEP inhibitors) had no significant effect on bradykinin-induced responses. Captopril and phosphoramidon did not potentiate isoproterenol (0.1 microM)-induced arteriolar dilation in the cheek pouch. Collectively, these data indicate that ACE and NEP each plays an important role in regulating bradykinin-induced vasorelaxation in the peripheral microcirculation in vivo.
本研究的目的是调查血管紧张素转换酶（ACE；EC 3.4.15.1）和中性内肽酶（NEP；EC 3.4.24.11）这两种广泛分布于外周微循环且能非常有效地降解激肽的膜结合金属酶，是否在体内调节缓激肽诱导的小动脉扩张。利用活体显微镜，我们在局部应用卡托普利（10.0微摩尔）和磷酰胺素（10.0纳摩尔）前后，测量了仓鼠颊囊内二级小动脉在缓激肽（0.1 - 10.0微摩尔）灌注期间的直径。我们发现每种抑制剂均显著增强了缓激肽诱导的小动脉直径增加（P < 0.05）。灌注其他蛋白酶抑制剂（不包括ACE和NEP抑制剂）对缓激肽诱导的反应无显著影响。卡托普利和磷酰胺素并未增强异丙肾上腺素（0.1微摩尔）诱导的颊囊小动脉扩张。总体而言，这些数据表明ACE和NEP各自在体内外周微循环中调节缓激肽诱导的血管舒张方面发挥重要作用。
