TY - JOUR
T1 - Altered neurovascular control of the resting circulation in human metabolic syndrome
AU - Limberg, Jacqueline K.
AU - Morgan, Barbara J.
AU - Sebranek, Joshua J.
AU - Proctor, Lester T.
AU - Walker, Benjamin J.
AU - Eldridge, Marlowe W.
AU - Schrage, William G.
PY - 2012/12
Y1 - 2012/12
N2 - 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), α1; clonidine (CL), α2). 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 α1-mediated vasoconstriction was inversely related to MSNA in control subjects (r= 0.5, P= 0.04); this balance between MSNA and α1 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 α2-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 α1-adrenergic responsiveness and increased α2 vasoconstriction may lead to reduced FBF, altered flow distribution, and/or severe hypertension with the progression toward diabetes and cardiovascular disease.
AB - 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), α1; clonidine (CL), α2). 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 α1-mediated vasoconstriction was inversely related to MSNA in control subjects (r= 0.5, P= 0.04); this balance between MSNA and α1 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 α2-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 α1-adrenergic responsiveness and increased α2 vasoconstriction may lead to reduced FBF, altered flow distribution, and/or severe hypertension with the progression toward diabetes and cardiovascular disease.
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U2 - 10.1113/jphysiol.2012.239780
DO - 10.1113/jphysiol.2012.239780
M3 - Article
C2 - 23027821
AN - SCOPUS:84870307844
SN - 0022-3751
VL - 590
SP - 6109
EP - 6119
JO - Journal of Physiology
JF - Journal of Physiology
IS - 23
ER -