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• W2027671563 abstract "Sildenafil (Viagra), a phosphodiesterase type-5 inhibitor used in treatment of male erectile dysfunction and pulmonary hypertension can induce cardioprotection through opening of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)). Recent studies suggest that activation of mitochondrial Ca(2+)-activated K(+) channels (mitoK(Ca)) also has anti-ischemic effects. However, the relative role of mitoK(Ca) and mitoK(ATP) in sildenafil-induced cardioprotection remains unknown. In the present study, adult male ICR mice were pretreated with sildenafil (0.71 mg/kg, i.p.) 24 h prior to 20 min of global ischemia followed by 30 min of reperfusion in Langendorff mode. Paxilline (blocker of K(Ca)) or 5-hydroxydecanoic acid (5-HD; blocker of mitoK(ATP)) was administered either 30 min before sildenafil or 10 min prior to ischemia. Treatment with sildenafil reduced infarct size, which was abolished by either paxilline or 5-HD. Furthermore, in vivo gene knockdown of beta1 subunit of K(Ca) (K(Ca)-beta1) using small interfering RNA (siRNA) administered 48 h before sildenafil injection blocked the infarct limiting effect of sildenafil. The protective effect of sildenafil was preserved in mice treated with non-target siRNA. Western blots demonstrated selective protein expression of K(Ca)-beta1 in cardiac mitochondria and the gene knockdown effect of siRNA on K(Ca)-beta1. The level of K(Ca)-beta1 protein was not upregulated following treatment with sildenafil. We conclude that both mitoK(Ca) and mitoK(ATP) play a critical role in triggering and mediating sildenafil-induced delayed cardioprotection. The results suggest that activation of mitoK(Ca) and mitoK(ATP) are crucial for maintaining mitochondrial homeostasis and reducing cell death in sildenafil-induced preconditioning against ischemia-reperfusion injury." @default.
• W2027671563 created "2016-06-24" @default.
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• W2027671563 date "2008-01-01" @default.
• W2027671563 modified "2023-10-09" @default.
• W2027671563 title "Essential role of mitochondrial Ca2+-activated and ATP-sensitive K+ channels in sildenafil-induced late cardioprotection" @default.
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• W2027671563 doi "https://doi.org/10.1016/j.yjmcc.2007.10.006" @default.
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