Epinephrine is a potent antagonist of the pedal edema induced in rats by subplantar injection of dextran ( 1 ) . Conceivably this could be due to one or more of several known, discrete actions of epinephrine: ( a ) vasoconstriction, ( b ) vasodilation, or ( c ) effects on certain "metabolic" processes such as glycogenolysis and lipolysis. The vasoconstrictor action of epinephrine is believed to be mediated via the hypothetical alpha adrenergic receptors (2), while the vasodilator and metabolic effects are most probably a result of beta adrenergic receptor stimulation although species differences appear to exist(3).Larsen and Lish(4) recently described the synthesis and beta adrenergic blocking activity of a series of phenethanolamines containing alkyl sulfonamide groups on the benzene ring. Three additional reports( 3,5,6) further describe the pharmacologic and toxicologic properties of two compounds, MJ 1998" and MJ 1999,t in that series. In particular, Kvam et aZ(3) reported on the effects of these beta receptor blocking agents on certain metabolic responses to catecholamines. For example, in the intact rat the compounds blocked epinephrine-induced hyperglycemia, but did not alter the elevation of plasma free fatty acids (FFA) induced by either epinephrine, norepinephrine, or isoproterenol. However, both MJ 1998 and MJ 1999 could inhibit catecholamine-induced FFA release in isolated rat adipose tissue. On the other hand the beta blocking agents antagonized both the hyperglycemia and the increases in plasma FFA in the intact dog.Since epinephrine effectively inhibits dextran-induced rat paw edema(l), it was of interest to determine whether beta adrenergic blockade could antagonize this action of epinephrine, and if so, whether it similarly af-* MJ 1998 = 4-(2-methylamino-l-hydroxypropyl) t M J 1999 = 4-(2-isopropylamino-l-hydroxy-niethanesulfonanilicle HCl.propyl) methanesulfonanilde HCI. fec t ed "non-adrenergic" vasodilators.Methods. Adult Wistar rats of either sex and weighing 140-160 g each were divided randomly into groups of 10 each. Certain groups received MJ 1999 orally one hour before a subcutaneous injection of epinephrine (as I-adrenaline, Eastman Kodak #3097). Others received only epinephrine. Fifteen minutes following the epinephrine injection all rats received subplantar injections of 0.1 ml of 6% dextran in physiological saline in the right hind paw, and 0.1 ml of saline contralaterally. One hour later the mean % of increase in edema of the dextran-over the saline-injected paws in each group was determined plethysmographically by mercury displacement( 7).The interactions of MJ 1999 and isoxsuprine or hydralazine were similarly examined. Also the effect of the alpha blocking drug, phentolamine, on inhibition by epinephrine was tested.Results. The data in Table I indicate that MJ 1999 can antagonize the inhibition of dextran-induced edema of the rat paw by epinephrine. The degree of effect of the beta adrenergic blocking agent is dose-dependent and approaches completeness when used with a submaxim...

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