Ando Makoto, Matsumoto Takayuki, Kobayashi Shota, Iguchi Maika, Taguchi Kumiko, Kobayashi Tsuneo
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Can J Physiol Pharmacol. 2018 Aug;96(8):839-844. doi: 10.1139/cjpp-2017-0557. Epub 2018 Mar 20.
The purpose of this study was to determine the relationship of K channels to endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries of 7-month-old spontaneously hypertensive rats (SHR). Upon inhibition of nitric oxide synthase and cyclooxygenase, ACh-induced EDHF-mediated relaxation was found to be weaker in SHR than in age-matched Wistar Kyoto rats (WKY). These relaxations in both group were attenuated by combined treatment with small-conductance and intermediate-conductance Ca-activated K channels (SK and IK) inhibitors, with the exception of relaxation resistant to inhibition of these channels in SHR (vs. WKY). Treatment with large-conductance Ca-activated K channels (BK) inhibitor specifically attenuated relaxation in SHR, but not in WKY. Protein expression of IK and SK in the arteries did not differ between the 2 groups, whereas ratio of sloβ1 subunit to α subunit of BK was increased in SHR (vs. WKY). These results suggest that EDHF-mediated relaxations in superior mesenteric arteries are impaired in SHR, and utilize components of BK in addition to SK/IK channel activities, that the increased participation of BK may be attributable to alterations in α and sloβ1 subunit ratio, and that components unrelated to K activity may also contribute to the difference between SHR and WKY arteries.
本研究的目的是确定钾通道与7月龄自发性高血压大鼠(SHR)肠系膜上动脉中乙酰胆碱(ACh)诱导的内皮依赖性超极化因子(EDHF)介导的舒张之间的关系。在抑制一氧化氮合酶和环氧化酶后,发现SHR中ACh诱导的EDHF介导的舒张比年龄匹配的Wistar Kyoto大鼠(WKY)弱。两组的这些舒张均通过小电导和中电导钙激活钾通道(SK和IK)抑制剂联合处理而减弱,但SHR中对这些通道抑制有抗性的舒张除外(与WKY相比)。大电导钙激活钾通道(BK)抑制剂处理特异性减弱了SHR中的舒张,但未减弱WKY中的舒张。两组动脉中IK和SK的蛋白表达无差异,而SHR中BK的sloβ1亚基与α亚基的比例增加(与WKY相比)。这些结果表明,SHR肠系膜上动脉中EDHF介导的舒张受损,除了SK/IK通道活性外还利用了BK的成分,BK参与增加可能归因于α和sloβ1亚基比例的改变,并且与钾活性无关的成分也可能导致SHR和WKY动脉之间的差异。