Effect of hypoxia on nerve-stimulation-induced release of noradrenaline from the rabbit heart.
The present study addressed the hypothesis that cardiac production of adenosine (ADO) and/or prostacyclin (PGI2) during hypoxia is augmented to a level sufficient to affect nerve-stimulation-induced release of noradrenaline (NA). Innervated rabbit hearts were perfused at high (95% O2) or low (8% O2) oxygen pressure. The effluxes of NA and purines from the heart were determined by HPLC and that of the PGI2 metabolite by radioimmunoassay. Five minutes of hypoxia elevated effluent purines (sum of ADO, inosine, and hypoxanthine) from 1.1 microM to 6.2 microM, but did not affect the outflow of NA. The ADO receptor antagonists THEO (100-200 microM) and 8PSOT (100 microM) given during hypoxia increased the evoked outflow of NA by 77% (P less than 0.01) and 37% (P less than 0.05), respectively. Indomethacin (30 microM, a prostaglandin synthesis inhibitor) reduced the efflux of PGI2 metabolite by 93% but did not per se affect NA outflow during simultaneous administration of THEO, either under normoxia or hypoxia. It is concluded that ADO, but not PGI2, plays a role in reducing transmitter release during hypoxia. In addition, hypoxia leads to an enhancement of transmitter release, probably unrelated to ADO or purines. The lack of effect of hypoxia alone on evoked outflow of transmitter seems to be the result of a combination of these two processes.
Wennmalm
M
M
Department of Physiology, Karolinska Institutet, Stockholm, Sweden.
D000241:Adenosine / Q000096:biosynthesis; D000818:Animals; D004558:Electric Stimulation; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006321:Heart / Q000294:innervation / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology
D013806:Theophylline; D011464:Epoprostenol; D000241:Adenosine; D009638:Norepinephrine; D007213:Indomethacin