Increasing evidence indicates that the enzyme creatine kinase (CK) is intimately involved in microvascular contractility. The mitochondrial isoenzyme catalyses phosphocreatine synthesis from ATP, while cytoplasmic CK, predominantly the BB isoenzyme in vascular tissue, is tightly bound near myosin ATPase, where it favours ATP production from phosphocreatine to metabolically support vascular contractility. However, the effect of CK gene inactivation on microvascular function is hitherto unknown. We studied functional and structural parameters of mesenteric resistance arteries isolated from 5 adult male mice lacking cytoplasmic BB-CK and ubiquitous mitochondrial CK (CK–/–) vs 6 sex/age-matched controls. Using a Mulvany Halpern myograph, we assessed the acute maximum contractile force with 125 mM K⁺ and 10^–5 M norepinephrine, and the effect of two inhibitors, dinitrofluorobenzene, which inhibits phosphotransfer enzymes (0.1 μM), and the specific adenylate kinase inhibitor P1, P5-di(adenosine 5′) pentaphosphate (10^–6 to 10^–5 M). WT and CK–/– did not significantly differ in media thickness, vascular elasticity parameters, or acute maximum contractile force. CK–/– arteries displayed greater reduction in contractility after dinitrofluorobenzene 38%; vs 14% in WT; and after AK inhibition, 14% vs 5.5% in WT, and displayed abnormal mitochondria, with a partial loss of the inner membrane. Thus, CK–/– mice display a surprisingly mild phenotype in vascular dysfunction. However, the mitochondrial abnormalities and greater effect of inhibitors on contractility may reflect a compromised energy metabolism. In CK–/– mice, compensatory mechanisms salvage energy metabolism, as described for other CK knock-out models.

中文翻译：

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BB-肌酸激酶和无处不在的Mt-肌酸激酶双敲除小鼠的抗动脉结构和功能。

越来越多的证据表明，肌酸激酶（CK）与微血管收缩密切相关。线粒体同工酶催化从ATP合成磷酸肌酸，而细胞质CK（主要是血管组织中的BB同工酶）紧密结合在肌球蛋白ATPase附近，在那里它有利于从磷酸肌酸生成ATP以代谢支持血管收缩。然而，迄今为止，CK基因失活对微血管功能的影响尚不清楚。我们研究了从5例缺乏细胞质BB-CK和普遍存在的线粒体CK（CK – / –）的成年雄性小鼠中分离出的肠系膜阻力动脉的功能和结构参数，与6个性别/年龄相匹配的对照相比。使用Mulvany Halpern肌电图，我们评估了125 mM K ⁺和10 mK的急性最大收缩力^–5  M去甲肾上腺素，和两种抑制剂，抑制磷酸转移酶（0.1μM）的二硝基氟苯和特定的腺苷酸激酶抑制剂P1，P5-二（腺苷5'）五磷酸（10 ^–6至10 ^–5） M）。WT和CK – / –在介质厚度，血管弹性参数或急性最大收缩力方面无显着差异。在二硝基氟苯38％后，CK – / –动脉的收缩力下降更大。相比WT中的14％；AK抑制后，WT中14％相对于5.5％，并显示线粒体异常，内膜部分丢失。因此，CK – / –小鼠在血管功能障碍中表现出令人惊讶的轻度表型。但是，线粒体异常和抑制剂对收缩力的更大作用可能反映了能量代谢受损。在CK – / –小鼠中，补偿机制可以挽救能量代谢，如其他CK基因敲除模型所述。