Sympatho-Adrenal Stimulation by Carbon Dioxide and the Inhibitory Effect of Carbonic Acid on Epinephrine Response

Abstract

Carbon dioxide serves as a potent stimulus to increase the titer of circulating sympatho-adrenal catechol amines in the cat. Using the denervated nictitating membrane as an assay method the CO 2 threshold for adrenal stimulus was determined to be about 15% concentration in alvcolar air. Adrenalectomy decreased by 60% the catechol amine titer initiated by 30% CO 2 , but hepatectomy was ineffective. The stimulant effect of CO 2 in this action was specific and was not dependent on the change in hydrogen ion concentration. The spinal cat was almost as responsive as the normal to CO 2 stimulus, but if the cord was destroyed only a very low catechol amine concentration could be detected with comparable stimulus. In the intact cat much of the inhibition of response to administered epinephrine by CO 2 is more apparent than real, because the CO 2 itself serves as a stimulus to raise the endogeneous epinephrine titer and each subsequently administered test dose of epinephrine was then examined against a background of hormone action. Because of the alinear shape of the epinephrine dose-response curve this can be misinterpreted as ‘inhibition.’ There was however, a direct CO 2 inhibition of epinephrine-induced smooth muscle contraction which was most apparent in the range 3–15% alveolar CO 2 . Sympathetically innervated and denervated structures were inhibited to the same degree.