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Altered neurovascular control of the resting circulation in human metabolic syndrome
Author(s) -
Limberg Jacqueline K.,
Morgan Barbara J.,
Sebranek Joshua J.,
Proctor Lester T.,
Walker Benjamin J.,
Eldridge Marlowe W.,
Schrage William G.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.239780
Subject(s) - microneurography , vasoconstriction , medicine , endocrinology , adrenergic , sympathetic nervous system , metabolic syndrome , vasodilation , blood pressure , heart rate , obesity , baroreflex , receptor
Key points• Young healthy adults exhibit a balance between muscle sympathetic nerve activity (MSNA) and α‐adrenergic‐mediated vasoconstriction such that those with higher MSNA exhibit lower vascular‐adrenergic responsiveness. • In contrast to healthy adults, the balance between MSNA and α 1 ‐adrenergic‐mediated vasoconstriction is lost in adults with metabolic syndrome. In addition, adults with metabolic syndrome exhibit increased α 2 ‐adrenergic responsiveness. • This study uncovered some of the earliest sympathetic–haemodynamic changes in the progression from metabolic syndrome to cardiovascular disease and diabetes. • Considering metabolic syndrome subjects were relatively young and free of overt cardiovascular disease, it is reasonable to speculate as the disease progresses the observed uncoupling between MSNA and α‐adrenergic responsiveness may lead to reduced whole‐limb blood flow, altered blood flow distribution, reduced glucose delivery and/or increased hypertension severity.Abstract Young healthy adults exhibit an inverse linear relationship between muscle sympathetic nerve activity (MSNA) and α‐adrenergic responsiveness. This balance may be reversed in metabolic syndrome (MetSyn) as animal models exhibit increased sympathetic activity and α‐mediated vasoconstriction. We hypothesized humans with MetSyn would demonstrate increased α‐adrenergic vasoconstriction and the inverse relationship between MSNA and adrenergic responsiveness would be lost. We measured MSNA (microneurography of the peroneal nerve) and forearm blood flow (FBF, Doppler ultrasound) in 16 healthy control subjects (31 ± 3 years) and 14 adults with MetSyn (35 ± 3 years; P > 0.05) during local administration of α‐adrenergic agonists (phenylephrine (PE), α 1 ; clonidine (CL), α 2 ). MSNA was greater in MetSyn subjects than in healthy controls ( P < 0.05). A group difference in vasoconstriction to PE was not detected ( P = 0.08). The level of α 1 ‐mediated vasoconstriction was inversely related to MSNA in control subjects ( r = 0.5, P = 0.04); this balance between MSNA and α 1 responsiveness was lost in adults with MetSyn. MetSyn subjects exhibited greater vasoconstriction to CL infusion as compared with healthy controls ( P < 0.01). A relationship between MSNA and α 2 ‐mediated vasoconstriction was not detected in either group. In summary, altered neurovascular control in human MetSyn is receptor specific. The observed uncoupling between MSNA and α 1 ‐adrenergic responsiveness and increased α 2 vasoconstriction may lead to reduced FBF, altered flow distribution, and/or severe hypertension with the progression toward diabetes and cardiovascular disease.