在糖尿病期间，L-精氨酸不能逆转受损的激动剂诱导的大分子外流增加。

L-arginine does not reverse impaired agonist-induced increases in macromolecular efflux during diabetes mellitus.

作者信息

Mayhan W G

机构信息

Department of Physiology and Bophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.

出版信息

Cardiovasc Res. 1997 Apr;34(1):215-22. doi: 10.1016/s0008-6363(97)00013-8.

DOI:10.1016/s0008-6363(97)00013-8

PMID:9217893

Abstract

OBJECTIVE

The first goal of this study was to determine the effect of diabetes mellitus on agonist-induced increases in venular macromolecular permeability of the hamster cheek pouch. The second goal was examine the role for an alteration in the availability of L-arginine to nitric oxide synthase in impaired agonist-induced increases in macromolecular permeability during diabetes.

METHODS

We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mw = 70 K) to examine macromolecular extravasation from post-capillary venules in non-diabetic and diabetic (2 weeks after injection of streptozotocin) hamsters in response to histamine and substance P. Increases in extravasation of macromolecules were quantitated by counting the number of venular leaky sites and by calculating the clearance (ml/s x 10(-6)) of FITC-dextran-70 K.

RESULTS

In non-diabetic hamsters, histamine (1.0 and 5.0 microM) and substance P (50 and 100 nM) increased permeability of the cheek pouch microcirculation to FITC-dextran-70 K. In contrast, histamine- and substance P-induced increases in macromolecular extravasation were markedly reduced in diabetic hamsters. Next, we investigated whether alterations in histamine- and substance P-induced changes in macromolecular extravasation in diabetic hamsters may be related to an alteration in the availability of L-arginine. We examined whether exogenous application of L-arginine (100 microM) could restore impaired histamine- and substance-P-induced increases in macromolecular extravasation in diabetic hamsters. We found that L-arginine potentiated agonist-induced increases in macromolecular extravasation in non-diabetic hamsters, but did not alter responses in diabetic hamsters.

CONCLUSION

These findings suggest that short-term diabetes mellitus alters agonist-induced alterations in microvascular permeability. The mechanism of altered microvascular permeability during diabetes mellitus does not appear to be related to an impaired availability of L-arginine.

摘要

目的

本研究的首要目标是确定糖尿病对仓鼠颊囊小静脉中激动剂诱导的大分子通透性增加的影响。第二个目标是研究在糖尿病期间激动剂诱导的大分子通透性增加受损时，L-精氨酸对一氧化氮合酶可用性改变所起的作用。

方法

我们使用活体荧光显微镜和异硫氰酸荧光素葡聚糖（FITC-葡聚糖；分子量 = 70K）来检测非糖尿病和糖尿病（注射链脲佐菌素2周后）仓鼠的毛细血管后小静脉中大分子的渗出情况，以响应组胺和P物质。通过计算小静脉渗漏部位的数量以及计算FITC-葡聚糖-70K的清除率（ml/s×10⁻⁶）来定量大分子渗出的增加。

结果

在非糖尿病仓鼠中，组胺（1.0和5.0微摩尔）和P物质（50和100纳摩尔）增加了颊囊微循环对FITC-葡聚糖-70K的通透性。相比之下，组胺和P物质诱导的糖尿病仓鼠大分子渗出增加明显减少。接下来，我们研究了糖尿病仓鼠中组胺和P物质诱导的大分子渗出变化是否可能与L-精氨酸可用性的改变有关。我们检测了外源性应用L-精氨酸（100微摩尔）是否能恢复糖尿病仓鼠中受损的组胺和P物质诱导的大分子渗出增加。我们发现L-精氨酸增强了非糖尿病仓鼠中激动剂诱导的大分子渗出增加，但并未改变糖尿病仓鼠的反应。