An Experimental Study of Nitric Oxide,Protein Kinase C and Bradykinin Trigger the Induction of Heat Shock Protein and Delayed Protection of Ischemic Preconditioning and a Clinical Study of Plasma Nitric Oxide Level sin Patients with Chronic Atrial Fibrill

In present study, we systemically researched the effects of nitric oxide (NO), protein kinase C (PKC) and bradykinin (BK) on induction of heat shock protein 72 (HSP72) and delayed protection of ischemic preconditioning (DPOP) in rabbits. We also examed plasma NO levels in patients with chronic atrial fibrillation (AF) and chronic heart failure (CHF) to discuss the role of NO in the pathophysiological processes of AF and CHF.1.Nitric oxide opens the second window of cardioprotection in ischemic preconditioning via induction of heat shock protein 72Objective To examine myocardial NO content after ischemic preconditioning (IP) and the inhibition of NO synthesis during IP on the induction of heat shock protein 72 (HSP72) and infarct size-limiting effect of the second window of cardioprotection. Methods Rabbits were subjected to 4 cycles of 5-min of coronary artery occlusion separated by 10-min reperfusion, or received a sham operation. Myocardial samples were taken immediately, 2 h and 4 h after IP to measured myocardial NO content. We injected L-NAME ( an inhibitor of NO synthase) intravenously 5 min before IP followed by its continuous infusion. Twenty-four hours after IP or the sham operation, the hearts were rapidly excised for assaying HSP72 expression or were subjected to 30 min coronary artery occlusion followed by 120 min reperfusion and then measured infarct size (IS). Results Myocardial NO content increased immediately after IP, and returned to normal 2 hafter IP, and which was blocked by L-NAME. Twenty-four hours after IP or the sham operation, immunoblotting revealed an increase in HSP72 protein levels in the IP group; this was blocked by L-NAME. IS of the IP rabbits was reduced as compared with the control. IS in the IP rabbits was elevated as a result of L-NAME treatment. Administration of L-arginine and L-NAME together reversed the effects of L-NAME on the induction of HSP72 and IS. The intravenous administration of SNAP (a NO donor) over 20-min increased the induction of HSP72 and reduced IS 24 h later. Conclusion These findings suggest that Myocardial NO synthesis increased during IP, and which may be involved in the induction of HSP72 and the opening of the second window of cardioprotection of IP.2. The role of protein kinase C in NO triggering the induction of HSP72 and DPOPoflPObjective To measure protein kinase C (PKC) activity after IP, and to observe the inhibition of NO synthesis and PKC on the PKC activity, the induction of HSP72 and DPOP of IP. Methods Rabbits were subjected to 4 cycles of 5-min of coronary artery occlusion separated by 10-min reperfusion, or received a sham operation. Myocardial samples were taken immediately after IP to measured PKC activity. We injected L-NAME and CHE (an inhibitor of PKC) intravenously 5 min before IP Twenty-four hours after IP or the sham operation, the hearts were rapidly excised for assaying HSP72 expression or were subjected to 30 min coronary artery occlusion followed by 120 min reperfusion and then measured IS. Results Myocardial ectosolic PKC activity increased immediately after IP, and which were blunt by L-NAME and CHE. Twenty-four hours after IP or the sham operation, immunoblotting revealed an increase in HSP72 protein levels in the IP group. This was blocked by L-NAME and CHE. IS of the IP rabbits was reduced as compared with the control, and which was elevated as a result of L-NAME and CHE pretreatment. The intravenous administration of SNAP also increased PKC activity immediately after drug administration and increased the induction of HSP72 and reduced IS 24 h later, and which was blocked by CHE. Conclusion These findings suggest that NO trigger the induction of HSP72 and DPOP by activating PKC.3. Bradykinin is involved in the delayed elevation of myocardial 5'-nucleotidase activity after IP and DPOP via increasing NO synthesisObjective To examine the effect of Bradykinin (BK) on NO synthesis in nonischemic myocardium, to measure myocardial 5'-nucleotidase activity 24 h after IP or BK pretreatment. and the...