THE SENSITIZATION OF VASCULAR RESPONSE TO "SYMPATHIN" BY COCAINE AND THE QUANTITATION OF "SYMPATHIN" IN TERMS OF ADRENALIN

Abstract

The action of NaHCO3, glycine, CaCl2 and cocaine on the rises in blood pressure produced by injections of epinephrine in Elliott''s preparation was studied in young decerebrate [male] cats. Of these cocaine proved to be the only effective sensitizer. Cocaine is more toxic to animals deprived of their adrenal glands than to intact animals. The higher the dose of cocaine, within limits set by toxicity, the more marked are its effects. Cocaine does not increase the effectiveness of epinephrine in accelerating the heart but it sensitizes smooth muscle to epinephrine. There is a close similarity between the action of cocaine as a sensitizer of smooth muscle to epinephrine and its role as sensitizer to the action of sympathin. This evidence favors the view of the identity of epinephrine and sympathin. In animals with the brain pithed, the adrenals extirpated, the sciatics cut and the sympathetic chains severed at the 3rd lumbar ganglion, stimulation of the lower portion of the sympathetic, which causes contraction of pilo-motor muscles, produces a. rise in blood pressure after cocaine injection which continues after the stimulus has ceased and which disappears very slowly (5 min.). Shutting off the circulation in the posterior part of the animal by pulling on a thread passed beneath the caya and aorta behind the renal vessels causes a quick rise of pressure and a quick fall when the thread is released; stimulating the lower end of the abdominal sympathetic chains during the pull on the thread produces a persistence of the rise in blood pressure after the thread is released and the stimulus stopped. The pressure falls slowly after this and is similar to the one mentioned above. The quantitation of sympathin in terms of epinephrine shows (on the average) that in a typical instance it is necessary to inject 2.4 cc. of epinephrine (1/500,000), the first 0.6 cc. at a rate of 0.1 cc. per 5 sec., the following 0.9 cc. at a rate of 0.1 cc. per 10 sec. and the last 0.9 at the rate of 0.1 cc. per 20 sec., in order to match the rise in pressure occasioned by half-min. stimulation of the sympathetic. The total amount of epinephrine thus injected is 0.000005 gm. The store of sympathin is limited under the conditions of the exp. The 1st stimulus is the most effective and the later stimuli (3 or 4) become rapidly incapable of producing any further results on the blood pressure.