Suzuki H, Gao X P, Olopade C O, Rubinstein I
Department of Medicine, University of Illinois at Chicago 60612-7323, USA.
Am J Physiol. 1996 Aug;271(2 Pt 2):R393-7. doi: 10.1152/ajpregu.1996.271.2.R393.
The purpose of this study was to determine whether vasoactive intestinal peptide (VIP) dilates resistance arterioles in the in situ systemic circulation and whether inhibitors of neutral endopeptidase (NEP) and angiotensin I-converting enzyme (ACE), two membrane-bound metalloenzymes that are widely distributed in the microcirculation and cleave and inactive VIP, potentiate this response. Using intravital microscopy, we found that VIP (0.05 and 0.1 nmol) induced significant vasodilation in the hamster cheek pouch (13 +/- 1 and 20 +/- 2% increase from baseline, respectively; mean +/- SE; P < 0.05). These responses were significantly potentiated by topical application of phosphoramidon and thiorphan, two relatively selective NEP inhibitors, but not by captopril, a relatively selective ACE inhibitor. Furthermore, suffusion of a mixture of proteinase inhibitors consisting of leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid to inhibit serine proteinases, including mast cell tryptase, aminopeptidases, and carboxypeptidase N, respectively, had no significant effects on VIP-induced responses. These data indicate that VIP elicits vasodilation in the in situ systemic microcirculation and that NEP modulates this response.
本研究的目的是确定血管活性肠肽（VIP）是否能使原位体循环中的阻力小动脉扩张，以及中性内肽酶（NEP）和血管紧张素I转换酶（ACE）的抑制剂——这两种广泛分布于微循环中且能裂解并使VIP失活的膜结合金属酶——是否能增强这一反应。通过活体显微镜观察，我们发现VIP（0.05和0.1纳摩尔）可使仓鼠颊囊产生显著的血管舒张（分别比基线增加13±1%和20±2%；平均值±标准误；P<0.05）。两种相对选择性的NEP抑制剂磷酰胺素和硫奥芬的局部应用可显著增强这些反应，但相对选择性的ACE抑制剂卡托普利则无此作用。此外，灌注由亮抑酶肽、贝抑素和DL-2-巯甲基-3-胍基乙基硫代丙酸组成的蛋白酶抑制剂混合物，以分别抑制包括肥大细胞类胰蛋白酶、氨肽酶和羧肽酶N在内的丝氨酸蛋白酶，对VIP诱导的反应没有显著影响。这些数据表明，VIP可引起原位体循环中的血管舒张，且NEP可调节这一反应。
