Penile Expression of Nitric Oxide Synthase Isoforms in the Type II Diabetic Rat

Lee, Jeong Oh; Park, Bu Kyung; Park, Hyun Jun; Park, Nam Cheol

Abstract

PURPOSE
Erectile dysfunction commonly occurs in men with diabetes mellitus. Nitric oxide synthase (NOS) is essential for regulation of penile erection, and the isoforms of NOS have significance in a variety of complications of diabetes. However, little is known about the localization, abundance, and changes in NOS in diabetes. Therefore, we characterized the localization and abundance of NOS isoforms and explored their relationships and how they are altered in diabetes.
MATERIALS AND METHODS
The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, which models type II diabetes mellitus, and the non-diabetic control Long-Evans Tokushima Otsuka (LETO) rat were used. We analyzed the distribution of NOS isoforms in the isolated corupus cavernosum of both LETO and OLETF rats by immunohistochemistry (IHC). The mRNA expression of NOS isoforms was also analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR).
RESULTS
The concentration of nitrite/nitrate in cavernosal homogenate was higher in diabetic rats than non-diabetic rats, but the difference was not statistically significant. There was a reduction of immunoreactivity for nNOS and eNOS as well as nNOS and eNOS mRNA expression (p<0.05) in diabetic rats, compared to non-diabetic rats. In contrast, the IHC stain showed that iNOS increased in both the endothelium and vascular smooth muscle in the diabetic rats, and the mRNA expression of iNOS gene was also up-regulated (p<0.05).
CONCLUSIONS
Change in the activity levels of NOS isoforms within the corpus cavernosum could be a major source of pathogenesis of erectile dysfunction in diabetes mellitus.