Effect of an aldose reductase inhibitor on altered sympathetic nerve responsiveness of isolated right atria in diabetic rats.
1. To determine the effects of an aldose reductase inhibitor (ARI) on diabetes-induced cardiac sympathetic disturbance, the effects of (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene] rhodamine (ONO-2235), an aldose reductase inhibitor, as well as insulin on the responsiveness to the transmural sympathetic nerve stimulation (TNS) and norepinephrine (NE) of isolated right atria of streptozotocin-induced diabetic rats were investigated. 2. The responsiveness to TNS of 8-week diabetic rats decreased, and those of 12-week diabetic rats severely decreased. The responses to NE also decreased 8 weeks or more after the induction of diabetes. 3. In 8-week diabetic rats, the insulin treatment completely restored the responsiveness to TNS, while ARI treatment partially restored the responsiveness to TNS. In 12-week diabetic rats, the single treatment with insulin or ARI only slightly restored the responsiveness to TNS, while the combination treatment with insulin and ARI almost completely restored the responsiveness to TNS in 12-week diabetic rats. 4. From the present results, the following may be concluded: Sympathetic nerve responses of right atria decreases in diabetic rats, and these changes may be related to hypoinsulinemia and abnormal polyol pathway. Although a serious sympathetic disturbance was only slightly improved by insulin or ARI, the combination of insulin and ARI produced more remarkable improvement of this disturbance.
Sato
N
N
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Hashimoto
H
H
Takiguchi
Y
Y
Nakashima
M
M
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006331:Heart Diseases / Q000209:etiology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012236:Rhodanine / Q000031:analogs & derivatives / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D053778:Thiazolidines
D007328:Insulin; D053778:Thiazolidines; C038131:epalrestat; D012236:Rhodanine; D000449:Aldehyde Reductase; D009638:Norepinephrine