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 [K[ATP]] 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 [K[ATP] opener; 45 mg/Kg, IP], glibenclamide [K[ATP] 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]