Guanylyl cyclase mediates ANP-induced vasoconstriction of murine splenic vessels.

Guanylyl cyclase mediates ANP-induced vasoconstriction of murine splenic vessels.
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鸟苷酸环化酶介导 ANP 诱导的小鼠脾血管收缩。

DOI:
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发表时间:
2003
期刊:
American Journal of Physiology. Regulatory Integrative and Comparative Physiology
影响因子:
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通讯作者:
S. Kaufman
S. Kaufman
中科院分区:
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文献类型:
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作者:
P. Andrew;S. Kaufman

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我们以前已经表明,ANP导致大鼠脾血管系统的差异性收缩(静脉大于动脉),这可能是通过阻断产生cGMP与A7195抑制。在本文中,我们报告了在鸟苷酸环化酶(GC)-A基因敲除小鼠的血管上进行的实验。从雄性GC-A缺陷型129 sv小鼠或年龄匹配的野生型对照小鼠中解剖小的脾动脉(直径约150微米)和静脉(直径约250微米),并固定在钢丝肌描记器中。在野生型小鼠中,ANP在静脉中比在动脉中表现出更高的效力(EC(50)值野生型小鼠:动脉,8 +/- 3 x 10(-9)M,n = 5 vs.静脉,6 +/- 4 x 10(-10)M,n = 5; P < 0.05)。与完整动脉相比,裸露动脉中ANP诱导的血管收缩的浓度-反应曲线也发生了明显偏移(EC(50)值:裸露动脉:5 +/- 3 x 10(-10)M,n = 5 vs.完整动脉,8 +/- 3 x 10(-9)M,n = 5; P < 0.05),即,裸露的血管反应性更强。相比之下,ANP在完整脾动脉、完整脾静脉或GC-A缺陷小鼠的裸露脾动脉中未引起张力较基线的显著变化,尽管这些血管对苯肾上腺素的张力确实显示出正常的浓度依赖性增加。我们的结论是,心钠素引起血管收缩脾血管内皮依赖性机制,介导鸟苷酸环化酶。
We have previously shown that ANP causes differential constriction of the splenic vasculature of the rat (veins greater than arteries), which may be inhibited by blocking the production of cGMP with A7195. In this paper, we report experiments done on vessels derived from guanylyl cyclase (GC)-A knockout mice. Small splenic arteries ( approximately 150-microm diameter) and veins ( approximately 250-microm diameter) were dissected from male GC-A-deficient 129sv mice or age-matched wild-type controls and mounted in a wire myograph. In the wild-type mice, ANP exhibited higher potency in the veins than in the arteries (EC(50) values wild-type mice: artery, 8 +/- 3 x 10(-9) M, n = 5 vs. vein, 6 +/- 4 x 10(-10) M, n = 5; P < 0.05). The concentration-response curve for ANP-induced vasoconstriction was also shifted leftward in denuded compared with intact arteries (EC(50) values: denuded artery: 5 +/- 3 x 10(-10) M, n = 5 vs. intact artery, 8 +/- 3 x 10(-9) M, n = 5; P < 0.05), i.e., the denuded vessels were more reactive. By contrast, ANP caused no significant change in tension from baseline in intact splenic arteries, intact splenic veins, or denuded splenic arteries derived from the GC-A-deficient mice, although these vessels did show normal concentration-dependent increases in tension to phenylephrine. We conclude that ANP causes vasoconstriction in the splenic vasculature by an endothelium-independent mechanism, mediated via guanylyl cyclase.
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