缓激肽对猪睫状动脉的舒张作用。一氧化氮和钾通道的作用。

Relaxation by bradykinin in porcine ciliary artery. Role of nitric oxide and K(+)-channels.

作者信息

Zhu P, Bény J L, Flammer J, Lüscher T F, Haefliger I O

机构信息

Laboratory of Ocular Pharmacology and Physiology, University Eye Hospital, Basel, Switzerland.

出版信息

Invest Ophthalmol Vis Sci. 1997 Aug;38(9):1761-7.

PMID:9286264

Abstract

PURPOSE

To assess the effects of K(+)-channel blockers on bradykinin-induced relaxations in porcine ciliary artery.

METHODS

Vascular isometric forces were measured with a myograph system. Ciliary vascular rings were precontracted with thromboxane A2 analog (U 46619, 10(-7) M) to assess dose-dependent (10(-10)-3 x 10(-6) M) bradykinin-induced relaxation after addition of one of the following: the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) or inactive enantiomer (D-NAME, 10(-4) M); the nonspecific K(+)-channel blocker tetra-ethylammonium (TEA, 10(-2) M); or the ATP-sensitive K(+)-channel blocker glibenclamide (10(-5) M). The effect of TEA on relaxations to the NO donor, sodium nitroprusside (SNP, 10(-10)-10(-4) M) was investigated. The membrane potential of vascular smooth muscle cells (VSMC) was recorded after exposure to bradykinin (2.5 x 10(-7) M).

RESULTS

Endothelium-dependent relaxations to bradykinin (maximal [max], 99% +/- 3%) were strongly inhibited by L-NAME (max, 39% +/- 4%, P < 0.01) and partially by TEA (max, 62% +/- 3%, P < 0.01) or glibenclamide (max, 77% +/- 4%, P < 0.01). Administration of glibenclamide plus L-NAME further suppressed bradykinin-induced relaxation (max, 23% +/- 6%; P < 0.01), whereas TEA and L-NAME (max, 6% +/- 2%; P < 0.01) abolished the relaxation. SNP relaxations were unaffected by TEA. Bradykinin had no effect on the membrane potential of VSMC.

CONCLUSIONS

In porcine ciliary artery, the endothelium-dependent relaxations to bradykinin are primarily mediated by NO and involve K(+)-channels. As only relaxations to bradykinin, but not those mediated by SNP, were inhibited by TEA, this implies that K(+)-channel blockers most likely affect the bradykinin-evoked NO production or release by the endothelium.

摘要

目的

评估钾通道阻滞剂对猪睫状动脉中缓激肽诱导的舒张作用的影响。

方法

使用肌动描记系统测量血管等长力。用血栓素A2类似物（U 46619，10⁻⁷ M）预收缩睫状血管环，在加入以下物质之一后评估剂量依赖性（10⁻¹⁰ - 3×10⁻⁶ M）的缓激肽诱导的舒张：一氧化氮（NO）合酶抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME，10⁻⁴ M）或无活性对映体（D-NAME，10⁻⁴ M）；非特异性钾通道阻滞剂四乙铵（TEA，10⁻² M）；或ATP敏感性钾通道阻滞剂格列本脲（10⁻⁵ M）。研究了TEA对向NO供体硝普钠（SNP，10⁻¹⁰ - 10⁻⁴ M）舒张的影响。在暴露于缓激肽（2.5×10⁻⁷ M）后记录血管平滑肌细胞（VSMC）的膜电位。

结果

L-NAME强烈抑制对缓激肽的内皮依赖性舒张（最大[max]，99%±3%）（最大，39%±4%，P<0.01），TEA（最大，62%±3%，P<0.01）或格列本脲（最大，77%±4%，P<0.01）部分抑制。给予格列本脲加L-NAME进一步抑制缓激肽诱导的舒张（最大，23%±6%；P<0.01），而TEA和L-NAME（最大，6%±2%；P<0.01）消除了舒张。SNP舒张不受TEA影响。缓激肽对VSMC的膜电位无影响。