Circnulatlion JUNE 1950VOL. I NO. 6 The Journal of the American Jeart Association Augmentation of Vasoactive Substances by

This investigation attempts to demonstrate the mechanism by which substances that block auto-nomic ganglionic transmission increase the pressor and depressor activities of a variety of (irugs. Short-lived hypertension and a high degree of vascular responsiveness is induced by combining cord destruction, inactivation of the carotid sinus mechanism and nephreetomn. The increased responsiveness is found to be due to removal of the compensatory nervous mechanisms which tend to oppose changes in blood pressure. It may be reduced or abolished by hepatectomy, se-vere hypotension and shock. B LOCKADE of transmission of nerve impulses within autonomic ganglia by tetraethylammonium chloride (TEAC) is now recognized as the chief action of this drug, as shown by the several penetrating in-vestigations of Acheson, Moe, Hoobler and Lyons.", 2, 3 4 5 This blockade, as we have demonstrated,6 7 results in augmentation of the cardiovascular pressor and depressor re-sponses to a variety of substances. Such increased responsiveness contrasts sharply with the refractory state of the vascular system in shock8 "and may have important significance because of the probability that disease of the heart and blood vessels may result from spe-cific changes in responsiveness to stimulation. The reasons for failure of TEAC to duplicate surgical sympathectomy is also worthy of in-vestigation.'0 The effects of TEAC, however, are not lim-ited to blockade of autonomic transmission. The initial depressor response is due to block-ade, but, as more and more of the drug is given, the depressor response gives way to a pressor one, caused by liberation from the liver of a noradrenaline-like substance. " At this stage of TEAC treatment, responses to many othe