title: Nitric Oxide is Necessary for Diazoxide Protection Against Ischemic Injury in Skeletal Muscle.
abstract: Ischemia reperfusion injury (IR injury) is a common problem in clinical conditions. Researches have frequently revealed that ATP- sensitive potassium (KATP) channels and nitric oxide plays a role in protection against ischemic injury in skeletal muscle. The present study aimed at evaluating the possible link between this two pathways. Sixty-eight male wistar rats, were pretreated with saline, diazoxide (KATP opener; 45 mg/Kg, IP), glibenclamide (KATP inhibitor; 5 mg/Kg), or L-NAME (iNOS inhibitor; 20 mg/Kg, IP) before 3 h ischemia and 2 h reperfusion. Activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and the level of malondialdehyde (MDA) and expression of iNOS were measured in muscle tissue. Tissue MDA content was significantly increased by IR (p < 0.001). Diazoxide significantly decreased the IR-induced elevation of tissue MDA level (p < 0.05) and Glibenclamide increased MDA (p < 0.05 vs. IR group). L-NAME inhibited the effect of diazoxide on decreasing MDA (p < 0.01 vs., diazoxide+IR group) and IR decreased the activity of SOD and CAT (p < 0.01), while pretreatment with diazoxide increased activity of SOD and CAT (p < 0.01). Glibenclamide decreased SOD and CAT activity after IR (p < 0.05). L-NAME pretreatment in diazoxide-treated rats abolished the effect of diazoxide on increasing the activity of SOD and CAT (p < 0.05 vs. Diaz+IR). Expression of iNOS was increased by IR (p < 0.01 vs. Sham group). Diazoxide significantly decreased iNOS expression after IR (p < 0.05 vs. IR). L-NAME significantly decreased iNOS expression after IR (p < 0.01) in diazoxide-treated rats (p < 0.01 vs. Diaz+IR). In conclusion, the results of present study suggested a NO dependent protective effect for diazoxide against muscle IR injury.
authors.affiliation: Department of Orthopedic Surgery, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Farahini
authors.forename: Marjan
authors.initials: M
authors.lastname: Ajami
authors.forename: Jalaledin
authors.initials: J
authors.lastname: Mirzay Razaz
authors.forename: Nahid
authors.initials: N
authors.lastname: Azad
authors.forename: Mansooreh
authors.initials: M
authors.lastname: Soleimani
authors.forename: Seyyed Abdulmajid
authors.initials: SA
authors.lastname: Ayatollahi
authors.forename: Nahid
authors.initials: N
authors.lastname: Abotaleb
authors.forename: Habibolah
authors.initials: H
authors.lastname: Peyrovi
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Pazoki-Toroudi
keywords: Diazoxide; Ischemia reperfusion; KATP channels; Nitric Oxide; iNOS