Mechanisms Underlying a Decrease in KCl-Induced Contraction after Long-TermSerum-Free Organ Culture of Rat Isolated Mesenteric Artery

[摘要] References(34)Cited-By(1)Organ culture of blood vesselis a better technique to investigate the long-term effects of drugs. However, somefunctional changes may occur from freshly isolated vessel (Fresh). Mammalian/mechanistictarget of rapamycin (mTOR) regulates smooth muscle differentiation and Ca2+mobilization. We thus investigated mechanisms of alteration in smooth muscle contractilityafter serum-free organ culture focusing on mTOR. Rat isolated mesenteric arteries werecultured for 5 days without (0% serum) or with rapamycin. In 0% serum, absolutecontraction by KCl significantly decreased from Fresh, which was significantly rescued byrapamycin. In 0% serum, mTOR expression significantly increased from Fresh, which wassignificantly rescued by rapamycin. In 0% serum, expression of myocardin, a key regulatorof smooth muscle differentiation markers, significantly decreased from Fresh, which wassignificantly rescued by rapamycin. However, the decrease in expression of contractileproteins, including SM22α and calponin, was not changed by rapamycin. Basalphosphorylation of calmodulin-dependent protein kinase II significantly increased in 0%serum, which was significantly rescued by rapamycin. In 0% serum, absolute contraction bycaffeine significantly decreased from Fresh, which was significantly rescued by rapamycin.In conclusion, expression of mTOR increased during serum-free organ culture of ratisolated mesenteric artery for 5 days, which may be at least partly responsible for thedecreased smooth muscle contractility perhaps due to the decrease in the storedCa2+ in smooth muscle.

[学科分类] 兽医学

[关键词] contractility;mammalian/mechanistic target of rapamycin;organ culture;vascular smooth muscle