Erectile Dysfunction In Diabetes Is Due To Selective Defect In The Brain

Background

Sexual dysfunction is a well-recognized consequence of diabetes mellitus in men. Erectile dysfunction, retrograde ejaculation and the loss of seminal emission have all been described by such patients. This study examined induced penile erection, yawning and stretch in diabetic rats. Male Sprague-Dawley rats treated with streptozotocin (STZ) to induce diabetes were used as they exhibit sexual and behavioral symptoms similar to those found in diabetic men with sexual dysfunction.

The researchers focused on the paraventricular nucleus (PVN) of the hypothalamus, located in the brain, an integration center between the central and peripheral nervous systems. The site is involved in numerous functions, including erectile function and sexual behavior, and is a primary site within the forebrain that has been implicated in penile erection. The investigators also examined central nitric oxide (NO within the PVN) which plays an important role in the neurotransmission of normal penile erection.

Penile erection is a behavioral response that occurs in response to the administration of N-methyl-D-aspartic acid (NMDA) within the PVN. At the same time, inhibition of NO synthase with NG-monomethly-L-argining (L-NMMA) prevents NMDA-induced erection. The researchers hypothesized that the blunted NMDA mediated responses in diabetes reflects an impaired NO mechanism within the PVN. The involvement of an NO mechanism in the NMDA mediated behavioral response was also explored.

Methodology

The rats were exposed to a light/dark cycle, with standard temperature and humidity levels. The animals were randomly selected to receive chemical injection of the streptozotocin (STZ) to induce diabetes. Those rats that did not receive STZ (vehicle injected) served as controls. The experiments began on each of the rats four weeks after the injections.

Four experiments were conducted. Experiment one examined the effect of L-NMMA on NMDA mediated behavioral responses in normal rats; experiment two measured behavioral responses to NMDA or sodium nitroprusside (SNP), an NO donor in both control and diabetic rats; the third experiment observed the effect of diabetes on nNOS protein in the PVN; the fourth experiment measured NMDA mediated behavioral responses in diabetic rats after restoring the nNOS protein in the PVN using viral gene transfer.

Results

The researchers found that:

• when L-NMMA was used to block NO production in the PVN, NMDA mediated penile erectile responses were blunted
• NMDA-induced erections were significantly blunted in diabetic rats compared with control rats
•  the nNOS protein levels in the PVN were decreased in rats with diabetes and
• restoring nNOS protein within the PVN of diabetic rats with viral gene transfer could alleviate the blunted NMDA induced erectile responses.
• Conclusion

The researchers conclude that erectile dysfunction in diabetes is due to a selective defect in the NO mechanisms within the PVN. This defect is a loss in the synthetic enzyme for the production of NO within the neurons of the PVN. Restoring this synthetic enzyme may have a significant therapeutic value for diabetic patients with ED.

The study, “Lack of Central Nitric Oxide Triggers Erectile Dysfunction in Diabetes,” was conducted by Hong Zheng, William G. Mayhan, and Kaushik P. Patel, Departments of Cellular and Integrative Physiology; and Keshore R. Bidasee, Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE. The results appear in the March 2007 edition of the American Journal of Physiology – Regulatory, Integrative and Comparative Physiology.