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tetro(lotoxin on vascular smooth muscle. J. Pharmacol. Exp. Then. 164: 60-74, 1968. In head-body cross-perfused dogs, procaine caused systemic hypotension only when it was applied to the body, indicating that the hypotension was due to an action of procaine some-where outside the brain. This conclusion is similar to an earlier one on the hypotension produced by tetrodotoxin. Using a gracihis muscle preparation with a vasculature isolated from the systemic circulation and perfused by a constant-volume pump with either the animal’s own blood or another animal’s blood, it was shown that small doses of procaine (1-5 mg/kg) and tetrodotoxin (0.5-0.8 ag/kg) caused a fall in the perfusion pressure. Since these doses did not block the reflex vasomotor effects on perfusion pressure caused by changes in systemic blood pressure or the effects of stimulating the sympathetic nerves, the fall in perfusion pressure was attributed to a direct relaxant effect on vascular smooth muscle. This conclusion is supported by the observations that after alpha or beta adrenergic blockade, or histamine blockade, the fall in perfusion pressure can still he produced by procaine and tetrodotoxin. Although it is widely known that procain