Effects of acidosis on anoxic and exocytotic noradrenaline release from the heart.
The effects of acidosis (pH 6.5) on the efflux of noradrenaline from the perfused heart of the rat have been studied. Acidosis does not influence the noradrenaline efflux induced by sympathetic nerve stimulation either in the presence or absence of neuronal uptake blockade. It is therefore unlikely that acidosis will contribute to the failure of nerve stimulation mediated noradrenaline release previously shown to occur during myocardial ischaemia. Acidosis exerts a biphasic effect on the noradrenaline efflux produced by substrate free anoxic perfusion with an inhibition of early noradrenaline overflow. Peak anoxic efflux of noradrenaline is greater when extracellular NaCl is replaced by Tris or sucrose in keeping with the hypothesis of carrier-mediated noradrenaline efflux. Marked early anoxic efflux occurs when extracellular NaCl is replaced by LiCl suggesting an additional mechanism of vesicular destabilization. Anoxic noradrenaline efflux is inhibited by amiloride (and ethylisopropyl amiloride) and it is proposed that the inhibitory effect of extracellular acidosis on early noradrenaline efflux also occurs by inhibition of the Na+ (Li+)/H+ antiporter leading to reduced Na+ (Li+) entry during the early phase of anoxia. At a later stage acidosis enhances anoxic noradrenaline efflux. This effect is postulated to be due to a reduction in the transvesicular pH gradient available for catecholamine storage within the storage vesicles.
Dart
A M
AM
Department of Medicine, University of Edinburgh, Scotland, UK.
Riemersma
R A
RA
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D005089:Exocytosis; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D009638:Norepinephrine