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首页> 外文期刊>Life sciences >Effect of age on the vasorelaxation elicited by cromakalim. Role of K+ channels and cyclic GMP.
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Effect of age on the vasorelaxation elicited by cromakalim. Role of K+ channels and cyclic GMP.

机译：年龄对克罗马卡林引起的血管舒张的影响。 K +通道和循环GMP的作用。

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摘要

The objective of this study was to investigate whether age induces changes on vasodilator response induced by cromakalim, an ATP-sensitive K+ (K(ATP)) channel opener, as well as the underlying mechanism involved in this possible alteration. For this purpose, aortic segments from young (3-5 months) and old (3 years) rabbits were used, which were precontracted with noradrenaline (NA, 1 microM). The vasodilator response induced by cromakalim (0.01-100 microM) was reduced in intact segments from old rabbits, and endothelium removal reduced and did not modify this effect in young and old animals, respectively. In both groups of animals, glibenclamide (10 microM), a blocker of K(ATP) channels, significantly reduced the response elicited by cromakalim, which was not modified by the large conductance Ca2+-activated K+ channel blocker charybdotoxin (ChTX, 0.4 microM). Acetylcholine (ACh, 10 microM) and sodium nitroprusside (SNP, 100 microM) induced a lesser vasodilator effect in aortic segments from old compared with young rabbits. In segments precontracted with NA, 10 microM ACh or 100 microM SNP similarly increased cGMP levels in both groups of animals. However, basal cGMP level was reduced in segments from old rabbits. Incubation with 8-bromo-cGMP (100 microM) increased the response induced by cromakalim in both groups of animals, reaching similar maximum values in young and old rabbits. The response induced by cromakalim plus 8-bromo-cGMP was markedly decreased by glibenclamide and unmodified by ChTx in both types of animals. These results suggest that aging decreases the vasodilator response to cromakalim, mechanism in which appears to be involved the maintained low cGMP levels observed in old rabbits, and that this messenger modulates the degree of K(ATP) channel activation.
机译：这项研究的目的是调查年龄是否引起由克罗卡林（一种ATP敏感性K +（K（ATP））通道开放剂）引起的血管舒张反应的改变，以及这种可能的改变所涉及的潜在机制。为了这个目的，使用了从幼兔（3-5个月）和大兔（3岁）的主动脉节段，它们预先与去甲肾上腺素（NA，1 microM）进行了收缩。克罗卡林（0.01-100 microM）诱导的成年兔完整节段中的血管舒张反应降低，内皮细胞去除率降低，并且在幼年和老年动物中均未改变这种作用。在两组动物中，格列本脲（10 microM）是K（ATP）通道的阻滞剂，均显着降低了由cromakalim引起的反应，而后者并未被大电导的Ca2 +激活的K +通道阻滞剂甲藻毒素（ChTX，0.4 microM）所修饰。与年幼兔相比，乙酰胆碱（ACh，10 microM）和硝普钠（SNP，100 microM）在老年主动脉段引起的血管舒张作用较小。在预先用NA收缩的片段中，两组动物中10 microM ACh或100 microM SNP相似地增加了cGMP水平。然而，成年兔的节段中基础cGMP水平降低。与8-溴-cGMP（100 microM）一起孵育可提高克罗卡林诱导的两组动物的反应，在成年和成年兔子中达到相似的最大值。在两种类型的动物中，格列本脲显着降低了克罗马卡林加8-溴-cGMP诱导的反应，而ChTx则未对其进行修饰。这些结果表明，衰老降低了对克罗马卡林的血管舒张反应，该机制似乎与在老年兔子中观察到的维持低cGMP水平有关，并且该信使调节了K（ATP）通道的活化程度。

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