Cardiac sympathetic neuropathy and effects of aldose reductase inhibitor in streptozotocin-induced diabetic rats.
Cardiac autonomic neuropathy can be a cause of sudden death in patients with diabetes mellitus. Clinical evaluation methods for diabetic cardiac sympathetic neuropathy have not been established. Using 125I-metaiodobenzylguanidine (MIBG) and streptozotocin (STZ)-induced diabetic rats, we evaluated cardiac sympathetic neuropathy and the effects of aldose reductase inhibitor (ARI).


METHODS
Myocardial MIBG uptake was measured 4 hr after injection in the following groups: control rats, rats treated with insulin or ARI (epalrestat, 100 mg/kg/day) from immediately to 4 wk after STZ injection and rats treated with insulin or ARI from 4-8 wk. Myocardial MIBG distribution and norepinephrine content were evaluated in the control and diabetic rats with or without ARI therapy started immediately after STZ injection.


RESULTS
Myocardial MIBG uptake was significantly lower in diabetic rats than in control rats; the reduction was marked in the subendocardial myocardium. Myocardial norepinephrine content was increased significantly in diabetic rats compared with control rats. Decreased MIBG uptake and increased norepinephrine content in diabetic myocardium were completely prevented by insulin therapy started immediately after STZ injection and partially, but significantly, by ARI administered from immediately after STZ injection. Heterogeneous MIBG distribution also disappeared with the ARI therapy. In contrast, diabetic rats treated with insulin or ARI therapy started 4 wk after STZ injection showed no improvement in MIBG uptake.


CONCLUSIONS
These results suggest that MIBG abnormalities observed in diabetic rats may reflect diabetic cardiac sympathetic neuropathy independently of cardiomyopathy, nephropathy or coronary heart disease secondary to diabetes and that MIBG imaging may be useful for clinical assessment of cardiac sympathetic neuropathy.
Kurata
C
C
Department of Medicine III, Hamamatsu University School of Medicine, Hamamatsu Red Cross Hospital, Japan.
Okayama
K
K
Wakabayashi
Y
Y
Shouda
S
S
Mikami
T
T
Tawarahara
K
K
Sugiyama
T
T
D019797:3-Iodobenzylguanidine; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy; D003929:Diabetic Neuropathies / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006321:Heart / Q000000981:diagnostic imaging*; D007328:Insulin / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D053778:Thiazolidines
D004791:Enzyme Inhibitors; D007328:Insulin; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D053778:Thiazolidines; D019797:3-Iodobenzylguanidine; C038131:epalrestat; D012236:Rhodanine; D000449:Aldehyde Reductase; D009638:Norepinephrine