TY - JOUR
T1 - Generalized and neurotransmitter-selective noradrenergic denervation in Parkinson's disease with orthostatic hypotension
AU - Sharabi, Yehonatan
AU - Imrich, Richard
AU - Holmes, Courtney
AU - Pechnik, Sandra
AU - Goldstein, David S.
PY - 2008/9/15
Y1 - 2008/9/15
N2 - Patients with Parkinson's disease (PD) often have manifestations of autonomic failure. About 40% have neurogenic orthostatic hypotension (NOH), and among PD+NOH patients virtually all have evidence of cardiac sympathetic denervation; however, whether PD+NOH entails extra-cardiac noradrenergic denervation has been less clear. Microdialysate concentrations of the main neuronal metabolite of nor-epinephrine (NE) and dihydroxyphenylglycol (DHPG) were measured in skeletal muscle, and plasma concentrations of NE and DHPG were measured in response to i.v. tyramine, yohimbine, and isoproterenol, in patients with PD+NOH, patients with pure autonomic failure (PAF), which is characterized by generalized catecholaminergic denervation, and control subjects. Microdialysate DHPG concentrations were similarly low in PD+NOH and PAF compared to control subjects (163 ± 25, 153 ± 27, and 304 ± 27 pg/mL, P < 0.01 each vs. control). The two groups also had similarly small plasma DHPG responses to tyramine (71 ± 58 and 82 ± 105 vs. 313 ± 94 pg/mL; P < 0.01 each vs. control) and NE responses to yohimbine (223 ± 37 and 61 ± 15 vs. 672 ± 130 pg/mL, P < 0.01 each vs. control), and virtually absent NE responses to isoproterenol (20 ± 34 and 14 ± 15 vs. 336 ± 78 pg/mL, P < 0.01 each vs. control). Patients with PD+NOH had normal bradycardia responses to edrophonium and normal epinephrine responses to glucagon. The results support the concept of generalized noradrenergic denervation in PD+NOH, with similar severity to that seen in PAF. In contrast, the parasympathetic cholinergic and adrenomedullary hormonal components of the autonomic nervous system seem intact in PD+NOH.
AB - Patients with Parkinson's disease (PD) often have manifestations of autonomic failure. About 40% have neurogenic orthostatic hypotension (NOH), and among PD+NOH patients virtually all have evidence of cardiac sympathetic denervation; however, whether PD+NOH entails extra-cardiac noradrenergic denervation has been less clear. Microdialysate concentrations of the main neuronal metabolite of nor-epinephrine (NE) and dihydroxyphenylglycol (DHPG) were measured in skeletal muscle, and plasma concentrations of NE and DHPG were measured in response to i.v. tyramine, yohimbine, and isoproterenol, in patients with PD+NOH, patients with pure autonomic failure (PAF), which is characterized by generalized catecholaminergic denervation, and control subjects. Microdialysate DHPG concentrations were similarly low in PD+NOH and PAF compared to control subjects (163 ± 25, 153 ± 27, and 304 ± 27 pg/mL, P < 0.01 each vs. control). The two groups also had similarly small plasma DHPG responses to tyramine (71 ± 58 and 82 ± 105 vs. 313 ± 94 pg/mL; P < 0.01 each vs. control) and NE responses to yohimbine (223 ± 37 and 61 ± 15 vs. 672 ± 130 pg/mL, P < 0.01 each vs. control), and virtually absent NE responses to isoproterenol (20 ± 34 and 14 ± 15 vs. 336 ± 78 pg/mL, P < 0.01 each vs. control). Patients with PD+NOH had normal bradycardia responses to edrophonium and normal epinephrine responses to glucagon. The results support the concept of generalized noradrenergic denervation in PD+NOH, with similar severity to that seen in PAF. In contrast, the parasympathetic cholinergic and adrenomedullary hormonal components of the autonomic nervous system seem intact in PD+NOH.
KW - Dysautonomia
KW - Multiple system atrophy
KW - Noradrenergic
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=55349121610&partnerID=8YFLogxK
U2 - 10.1002/mds.22226
DO - 10.1002/mds.22226
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C2 - 18661549
AN - SCOPUS:55349121610
SN - 0885-3185
VL - 23
SP - 1725
EP - 1732
JO - Movement Disorders
JF - Movement Disorders
IS - 12
ER -