Gene transfer of vasoactive intestinal polypeptide into the penis improves erectile response in the diabetic rat

Abstract

To determine the feasibility of transfecting penile corpora cavernosa with pcDNA3/vasoactive intestinal polypeptide (VIP) cDNA, which encodes for VIP in streptozotocin (STZ)-diabetic rats, to clarify whether transfection of VIP cDNA into the cavernosum affects the physiological response to cavernosal nerve stimulation, and whether this process would affect other organs in the diabetic rat model in vivo. pcDNA3/VIP cDNA was injected into the corpus cavernosum of STZ-induced diabetic Sprague-Dawley rats. The intracavernosal pressure (ICP) and response to electrical stimulation of the cavernosal nerve (15 Hz, 1.5 ms, 20 V, 1 min) were measured in subsamples of rats at 1, 3, 7 and 14 days after injection; after measuring the ICP the animals were killed, and penile, hepatic, renal artery and abdominal aorta tissue samples were frozen in liquid nitrogen and stored at -80 degrees C. The gene expression of VIP in all samples, assessed as the expression of VIP mRNA, was estimated using a semiquantitative reverse-transcription polymerase chain reaction. The mean amplitude of ICP and expression of VIP mRNA in the cavernosa of the VIP-treated rats was greater at 1, 3, 7 and 14 days after injection (P < 0.05) than in the control animals. There were no changes in the expression of VIP mRNA in hepatic, renal and abdominal aorta samples after injection (P > 0.05). VIP cDNA is easily incorporated into corpus cavernosum, and the expression is sustained for > or = 2 weeks in the penis in vivo. The transfer of VIP is capable of altering the physiologically relevant erectile response, as measured by an increase in the ICP after stimulating the cavernosal nerve. The intracorporal micro-injection of pcDNA3/VIP cDNA had little effect on the expression of VIP mRNA in other important organs.