Effect of Thiazolidinediones Administration on Neurochemical Composition of MPG Neurons Related to Erection in OLETF Rat / 대한해부학회지

ABSTRACT

The main transmitter substance mediating erection is the nitric oxide released from the vascular endothelial cells of corpus cavernosum and from the nonadrenergic, noncholinergic nerve endings. In addition, some neurotransmitters, such as acetylcholine or vasoactive intestinal polypeptide (VIP), have been reported to play an important role in mediating the erection. Thus, autonomic neuropathy may cause erectile dysfunction, and in reality, it occurs frequently in individuals with diabetes mellitus (DM), in which polyneuropathy, including both peripheral somatic sensorimotor neuropathy and autonomic neuropathy, develops usually. Thiazolidinedione (TZD) is an insulin-sensitizing agent used for the treatment of type 2 DM with insulin resistance, and has been reported to ameliorate nephropathy, decrease plasma glucose level and reduce blood pressure. However, the effect of this drug on the neuropathy related to erectile dysfunction has never been proved. In the present study, to evaluate the effect of TZDs on the neuropathy concerned with erectile dysfunction, we examined neurochemical changes of major pelvic ganglion (MPG) neurons in Otsuka Long Evans Tokushima Fatty (OLETF) rats, genetic models with non-insulin-dependent DM, after TZDs (pioglitazone and rosiglitazone) treatment. Age-matched nondiabetic Long Evans Tokushima Otsuka (LETO) rats were used as controls. Nitric oxide synthase (NOS), tyrosine hydroxylase (TH), VIP, and neuropeptide Y (NPY) contents were measured in MPG neurons of LETO, OLETF and pioglitazone- or rosiglitazone-treated OLETF rats by morphometry. Compared to the corresponding LETO group, number of TH-, NOS- and VIP-immunoreactive (ir) neurons decreased, while that of NPY-ir neurons, which modulate noradrenergic vasoconstriction of penile arteries, increased in the MPG of the OLETF group. After administration of pioglitazone- or rosiglitazone to OLETF rats for 23 weeks, these neurochemical changes were recovered to the control levels of the LETO group, although some variations were accompanied. These results suggest that TZDs treatment may be helpful for the treatment of autonomic neuropathy concerned with erectile dysfunction.