Simi Vincent | PubMed Health

PubMed2003

Neurovascular dissociation with paradoxical forearm vasodilation during systemic tyramine administration.

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, 0.15+/-0.05 versus 0.18+/-0.05 ng x dL(-1) x min(-1). As expected, forearm vascular resistance increased during the cold pressor test, but tyramine produced forearm vasodilation (4.5+/-1 versus -5+/-1 mm Hg x dL(-1) x min(-1), P<0.03) despite the increase in local norepinephrine spillover. In 6 additional subjects, plasma dopamine increased significantly during tyramine administration, from 11+/-3 to 662+/-105 pg/mL. CONCLUSIONS: Thus, systemic tyramine infusion evokes a significant increase in peripheral norepinephrine spillover, and this, paradoxically, is associated with local vasodilatation rather than vasoconstriction.

Adult↗

PubMed2002

The broader view: catecholamine abnormalities.

Norepinephrine (NE), a vital neurotransmitter in both the central and peripheral nervous systems, is synthesized by dopamine beta-hydroxylase (DBH) through the oxidation of dopamine (DA) to NE. DBH deficiency is a congenital disorder characterized by severe orthostatic hypotension, ptosis, and retrograde ejaculation. Biochemical features of the syndrome include elevated levels of dopamine, undetectable levels of DBH, undetectable tissue and circulating levels of NE and epinephrine. Molecular genetic analysis studies suggested that DBH deficiency is a Mendelian recessive disorder attributable to heterogenous mutations at the DBH locus. DBH deficiency has been treated effectively with L-threo-3,4-dihydroxyphenylserine (DOPS). DOPS is converted directly to NE through decarboxylation by L-aromatic amino acid decarboxylase (AADC), thereby bypassing DBH. Orthostatic intolerance is a syndrome characterized by lightheadedness, fatigue, altered mentation, syncope, and postural tachycardia. Biochemical features may include plasma NE concentration that is disproportionately high in relation to sympathetic outflow, decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists. A subset of OI patients has pathophysiologic features that have been associated with a genetic polymorphism. The coding mutation, A457P, occurs in one of the alleles of norepinephrine transporter gene of a proband with OI and her family. Alpha-methyl dopa, beta blockers and clonidine, a partial agonist of alpha2-adrenoceptor that acts centrally to reduce sympathetic outflow and lower blood pressure, have been effective in the treatment of this condition. The identification of the genetic polymorphisms involved in the synthesis, transport, storage, and metabolism of the catecholamines may provide new insights into the diagnosis and management of autonomic, cardiovascular, endocrine and psychiatric disorders.

Catecholamines↗