Activity and Thermosensitivity of Canine Cutaneous Veins after Inhibition of Monoamine Oxidase and Catechol-O-Methyl Transferase

Abstract

The lateral saphenous vein of the dog was perfused with homologous blood at constant flow. Changes in driving pressure were used to measure active changes in venous tone. Administration of tranylcypromine greatly reduced the activity of monoamine oxidase in the vein and increased its response to electric stimulation of the lumbar sympathetic chain and to norepinephrine infusions. Administration of pyrogallol (a catechol-O-methyl transferase inhibitor) also increased the response of the vein to adrenergic stimulation. These chemicals did not alter the increase in the sensitivity of the venous smooth muscle to sympathetic nerve impulses and infused norepinephrine produced by cooling the perfusate. Thus, the potentiating effect of local cooling on the response of the cutaneous veins to adrenergic stimulation cannot be explained by interference with the local enzymatic inactivation of catecholamines.ADDITIONAL KEY WORDS tranylcypromine pyrogallol catecholamine inactivation local temperature and venous reactions increased venous response to adrenergic stimulation monoamine oxidase in veins• Webb-Peploe and Shepherd (1-3) have shown that the cutaneous veins of the intact dog are highly sensitive to local changes in temperature: cooling the blood perfusing them augmented the venomotor response to a constant adrenergic stimulation and warming depressed the response. It appeared that an alteration in the sensitivity of the venous smooth muscle to both endogenous catecholamines released by sympathetic nerve stimulation and exogenous infused norepinephrine accounted for the venous responses to local temperature changes (3). A logical explanation for this sensitizing effect could be that the local inactivation of catecholamines is inFrom the Section of Physiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55901.This investigation was supported in part by U. S. Public Health Service Research Grant HE-5883 from the National Heart Institute.Dr. Vanhoutte is a U. S. Public Health Service International Fellow on leave from the State University of Ghent, Belgium.Received March 13, 1969. Accepted for publication September 4, 1969. fluenced by temperature, as suggested by the longer-lasting phase of increase in perfusion pressure and the delayed relaxation observed with local cooling. However, the potentiation by cold could not be explained by inhibition of catecholamine reuptake at the nerve terminals (4).Another possible pathway for local inactivation of catecholamines, at different levels of the release-reuptake process, is enzymatic degradation by monoamine oxidase and catechol-O-methyl transferase (5-10), so that one could consider the hypothesis that local temperature changes may interfere with the local inactivation of catecholamines. Indeed, in different sympathetically innervated systems it appeared that inhibition of one or both of those enzymes resulted in an increase of the response to adrenergic stimulation (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Arteries and veins are reported to conta...

Inhibition of adrenergic neurotransmission in isolated veins of the dog by potassium ions.

“…Although the washout of tritiated compounds in most cases is a reliable qualitative measure of the changes in intact [3H]norepinephrine, the present experiments indicate that changes in metabolite fraction sometimes can mask small changes in intact norepinephrine efflux. Although less importance can be attached to the quantitative changes observed in the amounts of norepinephrine metabolites, experiments such as these reported here confirm the presence of both the 0-methylation and the deamination pathway for the disposition of norepinephrine in dog's cutaneous veins (Vanhoutte & Shepherd, 1969;Osswald, Guimaraes & Colmbra, 1971;. In myogenically active arterial tissue, increases in external K+ concentration cause relaxation (Johansson & Bohr, 1966;Konold et al 1968;Gebert et al 1969;Brecht & Gebert, 1971) Brecht & Gebert, 1971).…”

“…min) (Vanhoutte & Shepherd, 1969;Osswald, Guimaraes & Colmbra, 1971;. In myogenically active arterial tissue, increases in external K+ concentration cause relaxation (Johansson & Bohr, 1966;Konold et al 1968;Gebert et al 1969;Brecht & Gebert, 1971); such relaxation cannot be I ;~+l +I +I +i +I +I +I +I +I +I +I +l +l +I +I +I +I Brecht & Gebert, 1971).…”

Inhibitors of prostaglandin synthesis augment beta-adrenergic responsiveness in canine coronary arteries.

“…However, tranylcypromine depressed, rather than augmented, 0-adrenergic relaxations. The other two major pharmacological actions of tranylcypromine, inhibition of monoamine-oxidase (Vanhoutte and Shepherd, 1969) and antagonism of a 2 -adrenoceptors (unpublished observations) should enhance rather than depress the inhibitory effect of catecholamines. Thus, cyclooxygenase products other than prostacyclin may also be involved in the blunting of /3-adrenergic responsiveness, especially when prostacyclin synthesis is inhibited.…”

In Memoriam: Paul M. Vanhoutte

“…Following postdoctoral studies in Ghent with Dr Leusen, Dr Vanhoutte in 1968 moved to the Mayo Clinic in Rochester, MN, USA, working under the mentorship of Irish‐born physiologist Dr John T. Shepherd (1919–2011) (Vanhoutte & Shepherd, ; Joyner, ; Vanhoutte et al . ).…”

“…MN, USA, working under the mentorship of Irish-born physiologist Dr John T. Shepherd (1919-2011) (Vanhoutte & Shepherd, 1969;Joyner, 2011;Vanhoutte et al 2012). After returning to Ghent in 1969, he accepted a position as Assistant Professor at the Mayo Clinic in 1972 (Fig.…”