Altered acetylcholine and norepinephrine concentrations in diabetic rat hearts. Role of parasympathetic nervous system in diabetic cardiomyopathy.
The concentrations of acetylcholine (ACh) as a parasympathetic marker and norepinephrine (NE) as a sympathetic marker were investigated in the hearts of rats 2, 4, and 8 wk after the induction of diabetes by an injection of streptozocin (STZ; 65 mg/kg i.v.). ACh and NE were measured by high-performance liquid chromatography with electrochemical detection. Diabetic rats showed low body weight and heart weight at 2, 4, and 8 wk and higher heart-to-body weight ratio and bradycardia at 8 wk, almost all of which were normalized after insulin treatment. Myocardial ACh and NE concentrations in the diabetic rats at 2 and 4 wk were not significantly different from those in age-matched control rats. However, ACh and NE concentrations in the diabetic rats at 8 wk significantly increased compared with the control rats. Diabetic rats at 8 wk also had increased myocardial choline concentration and choline acetyltransferase activity and decreased acetylcholinesterase activity. Insulin treatment normalized all of these changes in the diabetic rats. Thus, in STZ-induced diabetes (STZ-D), the concentrations of both cholinergic and noradrenergic neurotransmitters in the myocardium increased. The results of this study confirm a previously reported increase in sympathetic activity to the heart and also indicate that there is an increase in the synthesis and a decrease in the metabolism of ACh in STZ-D and that adequate insulin treatment normalizes these changes.
Akiyama
N
N
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Okumura
K
K
Watanabe
Y
Y
Hashimoto
H
H
Ito
T
T
Ogawa
K
K
Satake
T
T
D000109:Acetylcholine / Q000032:analysis*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000503:physiopathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000032:analysis* / Q000201:enzymology; D009638:Norepinephrine / Q000032:analysis*; D010275:Parasympathetic Nervous System / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D007328:Insulin; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine; D009638:Norepinephrine