Summary
To clarify the effects of hypoxia on stimulus-evoked noradrenaline release and on neuronal reuptake of the released noradrenaline, we examined the effects of hypoxia on contraction responses of rabbit thoracic aortic strips to transmural electrical stimulation and on the stimulation-evoked overflow of total [3H] and [3H]noradrenaline from the strips prelabelled with [3H]noradrenaline. This was done in the presence or absence of an inhibitor of neuronal uptake (cocaine). In a medium equilibrated with a gas mixture of 95% O2/5% CO2 (control), cocaine doubled the stimulation-evoked overflow of total [3H] and [3H]noradrenaline; there was a concomitant increase (130%) in contractions to electrical stimulation. At 0% O2 (95% N2/5% CO2, hypoxia), cocaine had no significant effects on either the stimulation-evoked overflow of total [3H] and [3H]noradrenaline or contractions. In the absence of the drug, hypoxia decreased the stimulation-evoked overflow of total [3H] and [3H]noradrenaline to 47% and 43%, respectively, of the control values, whereas these values were 31% and 28%, respectively, after exposure to cocaine. The inhibition by hypoxia of contraction responses to electrical stimulation was greater in the presence of cocaine than in its absence. These results show that hypoxia inhibits both noradrenaline release evoked by a given stimulus and neuronal uptake.
Similar content being viewed by others
References
Brandão F, Paiva MQ, Guimarães S (1980) The role of neuronal and extraneuronal systems in the metabolism of adrenaline and noradrenaline released from nerve terminals by electrical stimulation. Naunyn-Schmiedeberg's Arch Pharmacol 311: 1–7
Chance B, Williams GR (1955) A simple and rapid assay of oxidative phosphorylation. Nature 175:1120
Chappell JB (1964) The oxydation of citrate, isocitrate and cis-aconitate by isolated mitochondria. Biochem J 90:225–237
Dart AM, Riemersma RA, Schömig A, Ungar A (1987) Metabolic requirements for release of endogenous noradrenaline during myocardial ischaemia and anoxia. Br J Pharmacol 90:43–50
Iversen LL (1963) The uptake of noradrenaline by the isolated perfused rat heart. Br J Pharmacol 21:523–537
Langer SZ, Enero MA (1974) The potentiation of responses to adrenergic nerve stimulation in the presence of cocaine: its relationship to the metabolic fate of released norepinephrine. J Pharmacol Exp Ther 191:431–443
Lee K, Miwa S, Fujiwara M, Magaribuchi T, Fujiwara M (1987) Differential effects of hypoxia on the turnover of norepinephrine and epinephrine in the heart, adrenal gland, submaxillary gland and stomach. J Pharmacol Exp Ther 240:954–958
Lee K, Miwa S, Hayashi Y, Koshimura K, Taniguchi T, Orii Y, Fujiwara M (1988) Effects of hypoxia on contractile responses of rabbit aortic strips to transmural electrical stimulation. Naunyn-Schmiedeberg's Arch Pharmacol 338:275–281
Miwa S, Fujiwara M, Inoue M, Fujiwara M (1986) Effects of hypoxia on the activities of noradrenergic and dopaminergic neurons in the rat brain. J Neurochem 47:63–69
Muldoon SM, Vanhoutte PM, Tyce GM (1978) Norepinephrine metabolism in canine saphenous vein: prevalence of glycol metabolites. Am J Physiol 234:H235–14243
Rorie DK, Muldoon SM, Tyce GM (1980) Dispositon of norepinephrine during nerve stimulation in dog saphenous vein. Am J Physiol 239:14238–14246
Schömig A, Fischer S, Kurz T, Richardt G, Schömig E (1987) Nonexocytotic release of endogenous noradrenaline in the ischemic and anoxic rat heart: mechanism and metabolic requirements. Circ Res 60:194–205
Steel RGD, Torrie JH (1960) Principles and Procedures of Statistics. McGraw Hill, New York
Vanhoutte PM, Verbeuren TJ, Webb RC (1981) Local modulation of adrenergic neuroeffector interaction in the blood vessel wall. Physiol Rev 61:151–247
Wyce DG (1974) On the role of neuronal uptake (uptake1) in the inactivation of noradrenaline by aortic strips. Can J Physiol Pharmacol 52:1102–1109
Author information
Authors and Affiliations
Additional information
This work was supported by a Grant-in-Aid for New Drug Development from the Ministry of Health and Welfare of Japan and by a Grant from Smoking Research Foundation, Japan
Send offprint requests to S. Miwa at the above address
Rights and permissions
About this article
Cite this article
Lee, K., Miwa, S., Hayashi, Y. et al. Effects of hypoxia on noradrenaline release and neuronal reuptake in isolated rabbit thoracic aortic strips. Naunyn-Schmiedeberg's Arch Pharmacol 339, 503–508 (1989). https://doi.org/10.1007/BF00167252
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00167252