大鼠骨骼肌分离小动脉自发肌源性张力中的信号转导

Signal transduction in spontaneous myogenic tone in isolated arterioles from rat skeletal muscle.

作者信息

Bakker E N, Kerkhof C J, Sipkema P

机构信息

Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.

出版信息

Cardiovasc Res. 1999 Jan;41(1):229-36. doi: 10.1016/s0008-6363(98)00161-8.

DOI:10.1016/s0008-6363(98)00161-8

PMID:10325970

Abstract

OBJECTIVE

The mechanism of spontaneous myogenic tone was investigated in isolated arteriolar segments.

METHODS

Arterioles were isolated from rat cremaster muscle. Segments were endothelium-denuded and mounted in a pressure myograph at 75 mmHg. Under this condition, segments spontaneously constricted from a passive diameter of 167 +/- 3 to 82 +/- 4 microns (n = 41). The effects of several inhibitors were tested on the maintenance of myogenic tone.

RESULTS

Gadolinium (10(-6)-10(-4) M), a putative inhibitor of stretch-activated cation channels, was ineffective. The phospholipase C (PLC) inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC) induced a dose-dependent inhibition of tone. NCDC inhibited phenylephrine- (10(-6) M), but not potassium buffer-induced (100 mM) constriction. The protein kinase C (PKC) inhibitors staurosporine, chelerythrine and calphostin C inhibited myogenic tone in a concentration-dependent manner. At an intermediate concentration, calphostin C selectively inhibited phenylephrine-induced constriction. However, all PKC inhibitors abolished responses to phenylephrine and potassium buffer at higher concentrations. The cytochrome P450 inhibitor 17-ODYA (0.3-3 x 10(-6) M) did not inhibit myogenic tone.

CONCLUSIONS

No evidence was found for a role of gadolinium-sensitive, stretch-activated cation channels or cytochrome P450 metabolites. On the other hand, both PLC and PKC contribute to the maintenance of myogenic tone.

摘要

目的

研究离体小动脉节段自发性肌源性张力的机制。

方法

从小鼠提睾肌分离出小动脉。去除血管内皮后，将血管节段安装在压力肌动描记仪上，压力设定为75 mmHg。在此条件下，血管节段从被动直径167±3微米自发收缩至82±4微米（n = 41）。测试了几种抑制剂对肌源性张力维持的影响。

结果

推测的牵张激活阳离子通道抑制剂钆（10⁻⁶ - 10⁻⁴ M）无效。磷脂酶C（PLC）抑制剂2-硝基-4-羧基苯基-N,N-二苯基氨基甲酸盐（NCDC）诱导了剂量依赖性的张力抑制。NCDC抑制了去氧肾上腺素（10⁻⁶ M）诱导的收缩，但不抑制钾缓冲液（100 mM）诱导的收缩。蛋白激酶C（PKC）抑制剂星形孢菌素、白屈菜红碱和钙磷蛋白C以浓度依赖性方式抑制肌源性张力。在中等浓度下，钙磷蛋白C选择性抑制去氧肾上腺素诱导的收缩。然而，所有PKC抑制剂在较高浓度下均消除了对去氧肾上腺素和钾缓冲液的反应。细胞色素P450抑制剂17-ODYA（0.3 - 3×10⁻⁶ M）不抑制肌源性张力。