A Comparison of the Cardiovascular Effects of Biogenic Amines and Their Precursors in Newborn and Adult Dogs1’2

Piuvimii. , PHILIP J., JENNIFER M. H. LOGGIE AND THOMAS E. G m EY: A comparison of the cardiovascular effects of biogenic amines and their precursors in newborn and adult dogs. J. Pharmacol. Exp. Ther. 166: 293-298, 1969. There is relatively little information regarding the cardiovascular effects of the biogenic amines in newborn animals. In the present study the pressor and chronotropic responses to i.v. injections of norepinephrine, histamine, 5-hydroxytryptamine, their respective precursors and tyramine were compared in vagotomised, 1to 2-week-old puppies and adult dogs. Norepinephrine and its precursors produced increases in mean arterial pressure and heart rate in the newborns which were proportionately the same as those observed in the adults. Similarly the potency ratios of norepinephrine/dopamine/dopa, as reflected in the above parameters, were the same in both age groups. In addition, the time courses of the cardiovascular responses to dopamine, dopa and tyramine were generally equivalent in the newborn and adult dogs. Histamine produced a depressor response, whereas 5-hydroxytryptamine generally elicited a biphasic effect on mean arterial pressure in both groups of dogs. It is concluded that the circulatory alpha and beta adrenergic receptor systems in the newborn dog are quantitatively similar to the adult. The data also indicate that the cardiovascular system of the newborn dog is as sensitive as that of the adult to the effects of the other biogenic amines and their precursors. The role of the sympathetic nervous system in the regulation of the adult cardiovascular system has been extensively studied, but there is relatively little information regarding the state of development of the adrenergic nervous system or the cardiovascular effects of adrenergic drugs in newborn animals. For example, the comparative cardiovascular effects of norepinephnine and its precursors dopamine and dopa have not been systematically studied in newborn animals. There is even less information available from studies in young animals about the Received for publication September 6, 1968. ‘This study was supported by the Life Insurance Medical Research Foundation and by U.S. Public Health Service Grants HE-07392 and HE01506. ‘A preliminary report of this work was presented at the Fall Meetings of the American Society for Pharmacology and Experimental Therapeutics, August 27-31, 1967. (Pharmacologist 9: 199, 1967). ‘Postdoctoral Fellow in Pharmacology. ‘Research Career Development Awardee, Grant HE-K3-16008, National Institutes of Health, U.S. Public Health Service. cardiovascular effects of the other biogenic amines, histamine and 5-hydroxytryptamine. For these reasons and because of the possible implications of such information in the drug management of circulatory problems in newborn children, we have compared the pressor and chronotropic responses to norepinephrine (NE) and its precursors in newborn and adult dogs. Similarly we have examined the cardiovascular effects of histamine, 5-hydroxytryptamine and their respective precursors in newborns and adults because the endogenous forms of these amines may be involved in the physiologic regulation of the circulation. In addition, we have compared the circulatory effects of tyramine in newborns and adults in order to ascertain whether the newborn is able to release catecholamines in response to drugs. METHODS. The following drugs were studied: l-norepinephrine bitartrate (NE); 3,4-dihydroxyphenylethylamine hydrochloride (dopamine); 1-. 3,4-dihydroxyphenylalanine (dopa); tyramine hydrochloride; histamine dihydrochioride; l-histi-