Influence of the polyol pathway on norepinephrine transporter reduction in diabetic cardiac sympathetic nerves: implications for heterogeneous accumulation of MIBG.
OBJECTIVE
Cardiac scintigraphic studies using 123I-labeled metaiodobenzylguanidine ([123I]MIBG) have demonstrated heterogeneous myocardial accumulation of MIBG in diabetes. The accumulation has been found to correlate with a heterogeneous decrease in the expression of norepinephrine transporter (NET). In diabetic peripheral nerve tissue, polyol pathways are activated and cause nerve dysfunction and degeneration. However, there has been little research on the polyol pathway and cardiac sympathetic nerves. Therefore, to assess the influence of the polyol pathway on cardiac sympathetic nervous function, we investigated the regional accumulation of MIBG and NET protein expression in diabetic model rats treated with aldose reductase inhibitor (ARI) for the blockade of polyol pathways.


METHODS
Rats were given a single intravenous injection of streptozotocin (n=76, STZ-D rats). Starting the day after STZ injection, ARI was administered daily to 42 of the rats for 4 weeks (ARI-D rats). To assess the cardiac sympathetic nervous function, [125I]MIBG autoradiographic experiments were carried out. Finally, NET protein expression was assessed with a saturation binding assay.


RESULTS
The myocardial sorbitol concentration was significantly higher in STZ-D rats than in ARI-D rats. There was no heterogeneous accumulation of MIBG in ARI-D rats. There was a heterogeneous decrease of NET expression in STZ-D rats, but not in ARI-D or control rats.


CONCLUSIONS
The gathered data indicate that the enhanced polyol pathway correlates with the decrease in regional cardiac sympathetic nervous function, and this impairment may lead to the reduction of NET protein in cardiac sympathetic nerves of the diabetic inferior wall.
Kiyono
Yasushi
Y
Radioisotopes Research Laboratory, Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Kajiyama
Satomi
S
Fujiwara
Hiromi
H
Kanegawa
Naoki
N
Saji
Hideo
H
D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects / Q000294:innervation*; D008297:Male; D008657:Metabolic Clearance Rate; D009206:Myocardium / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012236:Rhodanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects; D013012:Sorbitol / Q000378:metabolism; D013311:Streptozocin; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*
D011108:Polymers; D019275:Radiopharmaceuticals; C024617:polyol; D019797:3-Iodobenzylguanidine; D013012:Sorbitol; D013311:Streptozocin; D012236:Rhodanine; D000449:Aldehyde Reductase