NOREPINEPHRINE AND DIHYDROXYPHENYLGLYCOL EFFLUXES FROM SYMPATHETIC-NERVE ENDINGS DURING HYPOXIA AND REOXYGENATION IN THE ISOLATED RAT-HEART

被引:12
作者
CHAHINE, R
NADEAU, R
LAMONTAGNE, D
YAMAGUCHI, N
DECHAMPLAIN, J
机构
[1] HOP SACRE COEUR,RES CTR,RECH SYST NERVEUX AUTONOME GRP,MONTREAL H4J 1C5,PQ,CANADA
[2] UNIV MONTREAL,FAC MED,DEPT PHYSIOL,MONTREAL H4J 1C5,PQ,CANADA
[3] UNIV MONTREAL,FAC MED,DEPT MED,MONTREAL H4J 1C5,PQ,CANADA
[4] UNIV MONTREAL,FAC PHARM,MONTREAL H4J 1C5,PQ,CANADA
关键词
HEART; NOREPINEPHRINE; HYPOXIA; MONOAMINE OXIDASE; UPTAKE I CARRIER;
D O I
10.1139/y94-085
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The present experiments were carried out in isolated rat hearts perfused according to the Langendorff method at a constant pressure of 10 kPa. The aim was to measure norepinephrine (NE) overflow and its deaminated metabolite dihydroxyphenylglycol (DOPEG) by changing the composition of the buffer perfusing the heart to simulate hypoxia. When aerobic and glycolytic pathways were simultaneously reduced, NE and DOPEG overflow increased 711 and 145%, respectively, after 30 min, compared with control values of 0.45 +/- 0.06 and 0.66 +/- 0.7 ng min(-1) g(-1) of heart (n = 8, p < 0.05). Whereas NE leakage decreased sharply after reoxygenation and glucose addition, DOPEG continued to increase up to 260% after 5 min of normal reperfusion. This mechanism was calcium independent and inhibited by 80% with desipramine (1 mu M), confirming the role of the uptake I carrier, which reversed its normal transport direction. Neuropeptide Y, a marker of exocytotic release, did not increase in the perfusate with the progression of hypoxia, which supports the hypothesis of a nonexocytotic release. Tyramine (1 mu M) significantly enhanced NE outflow by displacing the amine from its storage vesicles through a calcium-independent mechanism, indicating that a pool of NE was still available. In the presence of 1 mu M clorgyline (a monoamine oxidase A inhibitor) but not deprenyl (a monoamine oxidase B inhibitor), NE outflow increased 934% and DOPEG only 40% at 30 min (n = 6, p < 0.05 versus control hearts). It is concluded that both oxygen and glucose deprivation are necessary to induce a significant NE release from cardiac sympathetic nerve terminals and that monoamine oxidase A plays a principal role in NE deamination during hypoxia.
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页码:595 / 601
页数:7
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