TRANSIENT ISCHEMIA INHIBITS NONEXOCYTOTIC RELEASE OF NOREPINEPHRINE FOLLOWING SUSTAINED ISCHEMIA IN RAT-HEART - IS BRADYKININ INVOLVED

Previous studies have demonstrated that transient ischemia inhibits th e release of norepinephrine (NE) following a sustained ischemia. Howev er, the mechanism underlying this inhibition is unknown. Therefore, th is study was designed to investigate whether bradykinin (BK) may be in volved in the inhibition of NE release following ischemic precondition ing. The effects of transient ischemia, exogenous BK, and kinin recept or blockers on NE release after a prolonged ischemia were tested in th e isolated rat heart preparation. Three cycles of 5-min ischemia and r eperfusion resulted in the reduction of NE release from 115.3 +/- 14.5 to 51.6 +/- 9.3 pmol.g(-1) (p < 0.05) after 30 min of subtotal global ischemia. This effect was not prevented by the administration of eith er Lys-[Leu(8)]-des-Arg(9)-BK (1 mu mol.L-1), a B-1 antagonist, or HOE -140 (1 mu mol.L-1), a B-2 antagonist. Three cycles of 5-min BK or des -Arg(9)-BK infusion also resulted in a dose-dependent inhibition of NE release after 30 min of ischemia. The inhibitory effects of BK (1 mu mol.L-1) or des-Arg(9)-BK (0.5 mu mol.L-1) were blocked by Lys-[Leu(8) ]-des-Arg(9)-BK (1 mu mol.L-1), but not by HOE-140 (1 mu mol.L-1). The results show that transient ischemia and BK protect sympathetic nerve endings in the isolated rat heart The inhibition of NE release by pre treatment with BK is mediated by the activation of B-1 receptors, wher eas preconditioning provided by transient ischemia may be mediated by a different, yet unknown, mechanism in the rat heart.