[Effect of secretory human calcitonin gene-related peptide recombinant AAV on penile erection in streptozotocin-induced diabetic rat].

Objective: To determine whether recombinant adeno-associated virus-mediated overexpression of hCGRP in the corpus cavernosum can affect the continuous production of hCGRP in the penile tissue and enhance erectile responses in STZ-induced diabetic rats.Methods: Diabetes mellitus was induced by a single intraperitoneal injection of 60 mg/kg streptozotocin in male SD rats.VssHGCMV-hCGRP,VssCMV-GFP and rAAV solution were injected into the corporal cavernosum of STZ-induced diabetic rats,respectively.The corporal tissue was obtained from groups of 8 rats on day 5 post-injection,and the expressions of CGRP and GFP in cavernosal tissue were detected using immunohistochemisry and laser scanning confocal microscopy,respectively.Cavernosal tissue cAMP and cGMP levels were measured using rediaoimmunoassay.On day 5 post-injection,intracavernous pressure induced by electrostimulation of penile dorsal nerves was measured and recorded with a biological signal processing system in each group rat.Results: rAAV transduction efficiency of GFP reporter gene was measured by laser scanning confocal microscopy and was observed in the penile tissue,especially in the corporal cavernosum and the vessel 5 days after transfection with VssCMV-GFP.Immunohistochemistry showed that the CGRP increased in the corporal cavernosum.In addition,both cAMP and cGMP levels in the corpora cavernosa transfected with VssHGCMV-hCGRP were significantly increased,compared with controls[((48.4)±(6.5)) nmol/L and((21.2)±(13.6)) nmol/L vs((16.7)±(2.5)) nmol/L and((0.42)±(0.12)) nmol/L,respectively].More importantly,5 days after administration of VssHGCMV-hCGRP,a significant increase was observed in the erectile response to penile dorsal nerve stimulation in the diabetic rat[((60.5)±(4.5)) mm Hg vs((22.3)±(1.3)) mm Hg].Conclusions: This results demonstrate that rAAV-mediated transfer of the CGRP gene can increase production of endogenous CGRP,cAMP and cGMP in corpora cavernosa of STZ-induced diabetic rats.Moreover,overexpression of CGRP enhances ICP and the erectile response to penile dorsal nerve stimulation in the diabetic rat.Natl J Androl,2005,11(10):775-779