THE EFFECTS OF ACIDOSIS ON CHRONOTROPIC RESPONSES, NOREPINEPHRINE STORAGE AND RELEASE IN ISOLATED GUINEA-PIG ATRIA

¹ Department of Pharmacology, West Virginia University Medical Center, Morgantown, West Virginia

Spontaneously beating guinea-pig right atria were placed in baths at 30°C, pH of approximately 7.65 or 7.00, and cumulative dose-response curves were obtained with tyramine or norepinephrine (NE). Decreased pH had no effect on the spontaneous atrial rate. There was no change in the responses to NE. Chronotropic responses to tyramine, however, were markedly decreased at the lower pH. Since responses to NE were not affected by increased [H⁺], there was no acidosis-induced alteration in chronotropic adrenergic receptors. There was a significant decrease in atrial NE levels when the pH was reduced. H³-NE uptake and turnover studies were carried out. A pH-induced increase in atrial H³-NE turnover occurred and was not blocked by cocaine. At the lower pH, H⁸-NE retention was reduced and H³-deaminated metabolites increased. These data on NE uptake, storage and H³-deaminated metabolites in acidosis are interpreted as evidence of uptake inhibition at the level of storage granule. The changes in NE storage and decreased tyramine-induced release of H³-NE at pH 7.00 suggest a decrease in NE available for release by tyramine. This would explain the depressed chronotropic responses to tyramine in acidosis.