Does diabetes mellitus affect the progress of tolerance to isosorbide dinitrate (ISDN) in corporal tissue?

For erection to take place, the penile arteries and sinusoids have to dilat e, thereby increasing the blood flow into the penis. There is increasing ev idence that release of L-arginine derived nitric oxide (NO) from nonadrener gic-noncholinergic (NANC) nerves and from the sinusoidal endothelium is a m ajor event in penile smooth muscle relaxation and promotes the endogenous f ormation of cyclic guanosine monophosphate (cGMP). Nitrovasodilators can be attributed to the activation of soluble guanylate cyclase, resulting in an increase in intracellular level of cyclic guanosine monophosphate, but pro longed exposure to high levels of nitroglycerine and other organic nitroest ers induces tolerance against the cardiovascular effect. In this study, the aim was to determine the effect of diabetes on the corporal smooth muscle relaxant effect of ISDN and the effect of diabetes on the process of tolera nce to the drug. For this purpose, alloxan-induced diabetic rabbits were us ed to form diabetes group. The responses of the corpus cavernous strips obt ained from control and alloxan-induced diabetic rabbit were studied in orga n chamber. In conclusion, prolonged in vitro exposure of corpus cavernosum strips obtained from control and diabetic groups to high concentrations of ISDN caused significant desensitization to the relaxant effect the drug. So , prolonged exposure of corporal tissue to the agents like nitroglycerine, used for treatment of impotence, may render ineffective the therapy in diab etic erectile impotence. However, intolerance to nitric oxide provides a ra tionale for the concept of using nitro oxide agents (like SNP) in the treat ment of diabetic erectile dysfunction. (C) 2000 Academic Press.