THE INFLUENCE OF RESERPINE ON CARDIOVASCULAR RESPONSES TO NORADRENALINE, TYRAMINE, AND PITRESSIN DURING RESPIRATORY ACIDOSIS

Abstract

The responses of vascular smooth muscle (VSM) to noradrenaline are depressed during respiratory acidosis, but it has not been reported whether the depression is effected at the adrenergic receptor or distal to it in the contractile mechanism. This paper reports an attempt to make that determination. As respiratory acidosis has been shown to cause an increase in circulating catecholamines, the assumption was tested that the depression is due to partial occupancy of the adrenergic receptor sites by endogenous noradrenaline released by the hypercapnia. Hind limbs of reserpine-treated and untreated dogs and cats were perfused and the responses of the VSM to intra-arterial doses of noradrenaline and pitressin were tested before and during hypercapnia. Hypercapnia was induced by respiring the animals with 30% CO2 in O2. The responses of isolated rabbit aorta strips to noradrenaline were also tested before and during treatment with a high concentration of CO2 in the aerating gas mixture. Tyramine was used to test for depletion of the noradrenaline stores by reserpine treatment.The following observations were made: (a) The maximum responses of VSM to noradrenaline were not depressed during high-CO2 treatment. Therefore, the observed depression of responses to submaximal doses is probably due to an influence on the drug–receptor or coupling reactions rather than the contractile mechanism, (b) The depressive action was not confined to adrenergic drug–receptor reactions, as the responses to pitressin were also depressed by hypercapnia. Therefore, the depression was probably located between the drug–receptor reaction and the contractile mechanism in some coupling reaction common to the two drugs. Partial occupancy of the adrenergic receptors did not appear to be the cause of the depression, (c) Tyramine appeared to have a direct effect on the VSM of reserpine-treated dogs, (d) Reserpine potentiated the responses of the VSM of dogs to tyramine and pitressin as well as to noradrenaline, (e) Reserpine reversed the effects of hypercapnia on the responses of the cats to noradrenaline. During hypercapnia in reserpine-treated cats the responses to noradrenaline were potentiated. It is proposed that hypercapnia may depress the responses of VSM to noradrenaline by influencing the availability of calcium for the contractile reaction.