NOREPINEPHRINE INDUCES CARDIAC HEAT-SHOCK-PROTEIN-70 AND DELAYED CARDIOPROTECTION IN THE RAT THROUGH ALPHA(1)-ADRENOCEPTORS

Objective: Previous studies have demonstrated that norepinephrine (NE) confers immediate cardioprotection against ischemia and reperfusion i njuries. The present study rests the hypothesis that in vivo treatment with NE induces delayed cardioprotection against postischemic dysfunc tion in the rat heart which is associated with expression of c-Eos and heat shock protein (HSP) 70 in the myocardium. Methods: Rats were tre ated with NE (3.1 mu mol/kg, ip) and hearts isolated and perfused with a modified Langendorff technique 2 or 24 h after injection. Left vent ricular developed pressure (LVDP) and left ventricular end-diastolic p ressure (LVEDP) were recorded during 25 min normothermic global ischem ia and 40 min reperfusion. Total RNA was extracted from left ventricul ar tissue at various time paints and Northern hybridization was applie d co detect c-fos and HSP70 mRNAs. Expression and distribution of c-fo s and HSP72 proteins in tile myocardium were examined by immunohistoch emical staining, Results: In vivo NE treatment improved postischemic r ecovery of both LVDP and LVEDP in the hearts isolated at 24 h after tr eatment but not in those isolated at 2 h. LVDP was 68.9 +/- 4.8 mmHg i n NE 24 h group at the end of reperfusion in comparison to 43.6 +/- 2. 9 mmHg in saline control group (P < 0.01). Pretreatment with prazosin abolished NE-induced cardioprotection while propranolol pretreatment h ad no effect. Northern analysis demonstrated rapid and transient incre ases in c-ibs and HSP70 mRNAs in the myocardium after NE treatment. Ac cumulation of c-fos protein was observed at 3 h and increased amount o f HSP72 protein was demonstrated at 24 h in the myocardium. Pretreatme nt of rats with prazosin eliminated NE-induced increase in cardiac HSP 70 mRNA, Conclusions: The results suggest that in vivo treatment with NE upregulates the expression of c-fos and HSP70 in the myocardium and induces delayed protection against postischemic myocardial dysfunctio n in the isolated rat heart, Induction of both the expression of cardi ac HSP70 and the delayed cardioprotection by NE appears to be mediated by alpha(1) adrenoceptors.