Objective To determine whether a defect in vasoactive intestinal pepti
de (VIP)-mediated vasodilatation underlies diabetic impotence. Materia
ls and methods Rats treated with streptozotocin for 8 weeks developed
diabetes, as shown by hyperglycaemia and glycosuria, and had significa
nt impairment of sexual function, as determined by tests of sexual beh
aviour. The VIP content of the penis and major pelvic ganglion, the VI
P release by the penis in vitro and the responsiveness of the vasculat
ure of the penis in vivo to intracavernous VIP injection were determin
ed. Results In diabetic rats, the VIP content of the major pelvic gang
lion and penis was markedly increased, while the acetylcholine content
of the penis was normal. The amount of VIP released in vitro by high
potassium concentration or veratridine was similar for penile tissue s
lices of normal and diabetic rats. Intracavernous injection of VIP ind
uced erection in the control rats but not in diabetic rats, whereas in
tracavernous injection of the adenylate-cyclase activator forskolin pr
oduced erection in both control and diabetic rats. Conclusion Because
VIP induces vasodilatation by activating adenylate cyclase, and forsko
lin produced erection in the diabetic rats, the failure of VIP to prod
uce erection in these rats is unlikely to be due to a defect in the se
cond-messenger mechanism or in the properties of vascular smooth muscl
e. Thus, a defect at the level of the VIP receptor or of the associate
d G-protein possibly explains the failure of intracavernous VIP to pro
duce erection in the diabetic rats. Hence, an abnormality in VIP is a
component of sexual dysfunction in the diabetic rat and the defect is
at the level of the VIP receptor or associated G-protein.