The hemodynamic response of man to nor-epinephrine and epinephrine and its relation to the problem of hypertension

Abstract

Nor-epinephrine (nor-adrenaline, arterenol, amino-ethanolcatechol) is a primary amine identical with epinephrine except for the absence of a methyl group on the nitrogen atom. (Fig. 1.) It was first synthesized by Sto1z3? in 1904. Recently it has been suggested as a possible precursor of epinephrine in vivo5 since it has been shown that methylation occurs readily in the body.” The levo-isomer, possessing approximately twice the activity of the optically inactive preparation, became available in 1948 following resolution of the racemic mixture by Tainter and his group.38 The consistency with which the actions of nor-epinephrine reproduce those of stimulation of sympathetic excitor nerves has led competent investigators to the conclusion that it may be sympathin E, as first suggested by Bacq. 2 In support of this hypothesis Stehle and Ellsworth3’j and Greer and his co-workers20 demonstrated the striking similarity between the effects of nor-epinephrine and those produced by stimulation of the hepatic sympathetic nerves. These observations have been confirmed by von Euler1*~i3 and Gaddum and Goodwin.i8 The strongest evidence in favor of this assumption was von Euler’s demonstration in 1946 of a substance in mammalian adrenergic nerves indistinguishable from nor-epinephrine by biologic and crude chemical tests.‘**13 The thoracic and lumbar sympathetic chain and the splenic periarterial nerves of cattle were particularly suitable sources and contained the equivalent of 10 to 25 pg. of d,l-nor-epinephrine per Gm. of tissue. This substance differed from epinephrine in its blood pressure action following ergotamine. Ergotamine reverses the pressor effect of epinephrine but not of nor-epinephrine. This substance differed likewise from epinephrine in its action on the non-pregnant cat uterus in that relaxation was inconspicuous. It has been assumed that each of the transmitters, epinephrine and nor-epinephrine, carries excitor or inhibitor functions exclusively. But this does not appear to be so because excitor functions are carried not only by nor-epinephrine but also by epinephrine. Epinephrine has been proved to be the transmitter of sympathetic excitation in