Neurovascular Dissociation With Paradoxical Forearm Vasodilation During Systemic Tyramine Administration

Abstract

Background-Despite the widespread use of tyramine as a pharmacological tool to assess the effects of norepinephrine release from sympathetic nerve terminals, its vascular effects are not adequately characterized. In particular, previous results indicate that intravenous tyramine produces little if any systemic vasoconstriction, suggesting that tyramine does not cause significant norepinephrine release from sympathetic nerves innervating peripheral vascular beds. To test this hypothesis, we determined the effects of intravenous tyramine on local forearm norepinephrine spillover and vascular resistance. Methods and Results-Seven healthy subjects were studied with systemic and local forearm norepinephrine spillover and forearm blood flow at baseline, during systemic tyramine infusion, and after sympathetic stimulation induced by the cold pressor test. Tyramine infusion caused a significant increase in systemic and forearm norepinephrine spillover. The amount of norepinephrine released into the forearm by tyramine was similar to that caused by cold pressor stimulation, 0.15Ϯ0.05 versus 0.18Ϯ0.05 ng · dL Ϫ1 · min Ϫ1 . As expected, forearm vascular resistance increased during the cold pressor test, but tyramine produced forearm vasodilation (4.5Ϯ1 versus Ϫ5Ϯ1 mm Hg · dL Ϫ1 · min

An investigation of components of variance and tachyphylaxis in a placebo‐controlled intravenous tyramine study

“…This may not have been sufficient to distribute the tyramine into the circulation as effectively as an infusion. The finding of no significant rise in diastolic blood pressure or heart rate associated with the increase in systolic blood pressure is consistent with baroreflex buffering [7].…”

Clinical Assessment of Norepinephrine Transporter Blockade Through Biochemical and Pharmacological Profiles

“…CYP2D6 exhibits variable and heterogeneous expression in individuals. 11 5-HT transporter inhibitors might have an effect to reduce plasma NE in contrast to …”

Functional effects of cardiac sympathetic denervation in neurogenic orthostatic hypotension

“…[16][17][18][19][20] Sympathetic nerves take up tyramine via the cell membrane norepinephrine transporter. Tyramine in the axoplasm is then taken up into vesicles via the vesicular monoamine transporter, and in the vesicles tyramine displaces norepinephrine.…”

“…Although one might presume that tyramine increases blood pressure via generalized vasoconstriction and increased total peripheral resistance, it appears that most of the pressor response to tyramine depends on increased cardiac output, from increased stroke volume, in turn from increased myocardial contractility or increased venous return to the heart. [18,20] Others have reported forearm vasodilation in response to systemic tyramine administration, which would tend to decrease total peripheral resistance. Dopamine contamination of infused tyramine probably confounded the previously published results [19,21]; however, even infusion of uncontaminated tyramine seems to increase blood pressure via an increase in cardiac output.…”