الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 230 |  |  |
| | | from | 230 | | |
Abstract
Penile erection is a neurovascular event mo¬dulated by psychological and hormonal factors. At the molecular level, nitric oxide (NO) is the principal neurotransmitter involved in tumescence.
Calcitonin gene-related peptide (CGRP) is an important neuropeptide involved in penile erection. It is present in the central and peripheral nervous system, mainly in close approximation with blood vessels. CGRP is a potent arterial and venous vasodilator that acts directly on the smooth muscles to stimulate adenylate cyclase enzyme. The resulting rise in cAMP activates protein kinase A (PKA), which probably phosphorylates and opens K channels, leading to muscular relaxation.
Diabetes mellitus is a metabolic disease that leads to erectile dysfunction on the long run. The exact pathogenesis of diabetic erectile dysfunction remains to be completely understood. Both vasculopathy and neuropathy have been incriminated. However, previous studies failed to clarify which is the first or the predominant cause of diabetic erectile disturbance.
The aim of this study was to evaluate the early changes in CGRP expression and the histopathological changes occurring in diabetic rats penile tissues.
The present study was conducted on fifty adult male Sprague Dawly rats. The control group (Group I) involved 10 rats with intraperitoneal injection of saline. While Group II involved 40 rats that received a single intraperitoneal injection of streptozotocin (STZ).
Group II:40 rats were further subdivided into 4 subgroups:
Group IIa: 10 diabetic rats sacrificed after 2 weeks of induction of DM.
Group IIb: 10 diabetic rats sacrificed after 4 weeks of induction of DM
Group IIc: 10 diabetic rats sacrificed after 6 weeks of induction of DM
Group IId: 10 diabetic rats sacrificed after 8 weeks of induction of DM.
At the end of experimental period the followings were evaluated:
2- Fasting blood glucose level.
2- Tissue level of calcitonin gene related peptide .
3- Pathological changes occurring in the penile tissue.
The results revealed that the level of CGRP started to increase significantly in the diabetic rats 4 weeks after induction of DM and kept on increasing 6 weeks after induction of DM. However, no further significant increase in the level of CGRP occurred in the 8th week of DM compared to the 6 th week.
Regarding the histopathological changes, gradual flattening of the endothelium of the corpus cavernosum blood vessels started from the 2nd week till complete loss. The changes in the smooth muscles started as decreased smooth muscle mass at the 2nd week and progressed to partial replacement by fibrous tissue and even complete hyalinization in 70% of rats at 8 weeks. The vessel wall thickness of the affected vasculature decreased in a time progressive manner starting from the 4th week after induction of DM till the end of the study. There was a correlation between the rise in the CGPR level at 4 and 6 weeks after induction of DM and the histopathological changes in endothelium and smooth muscles.
The previous results showed that, diabetes mellitus is characterized by progressive loss of normal endothelium and smooth muscle cells from the corpus cavernosum. The early compensatory increase in the level of CGRP may play an important role in diabetes-induced fibromuscular changes which finally ends by deterioration of erectile function
Our study support the hypothesis that vasculopathy is the primary pathology in diabetic erectile dysfunction since it occurs earlier than neuropathy and may affect vasa nervosa. Furthermore, neuropathy may perpetuate vasculopathy since increased level of CGRP is associated with changes in smooth muscle type