Cyclic adenosine monophosphate and cyclic guanosine monophosphate-phosphodiesterase isoenzymes in human vagina: Relation to nitric oxide synthase isoforms and vasoactive intestinal polypeptide-containing nerves

Abstract

Objectives To evaluate the distribution of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) phosphodiesterases (PDEs) in relation to nitric oxide synthase isoforms and vasoactive intestinal polypeptide (VIP) in specimens of the human vagina. Nitric oxide and VIP, mediating biologic signals through cGMP and cAMP, have been assumed to be involved in the control of vaginal smooth muscle. Methods Immunohistochemical techniques were applied to sectioned specimens of the human vaginal wall to evaluate the presence of the PDE isoenzymes 3, 4, 5, and 10 in relation to neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and VIP. Results Immunoreactivity (IR) for cAMP-degrading PDE-4 was observed in the vaginal nonvascular smooth musculature, as well as in the wall of subepithelial arteries. VIP-IR nerves innervated the smooth muscle portion of the vaginal wall and also formed a subepithelial network. Immunoreactivity specific for PDE-5 was also registered in vascular and nonvascular vaginal smooth muscle. Immunosignals for eNOS were detected in the endothelial lining of arteries containing PDE-5-IR smooth muscle cells. These arteries were supplied by nNOS-IR nerve fibers. PDE-10-IR smooth muscle cells were located in muscle bundles of the vaginal wall. Conclusions Our study revealed immunoreactivity specific for PDE-4, PDE-5, and PDE-10 in the vascular and nonvascular smooth muscle of the vagina. Immunosignals for PDE-4 and PDE-5 were also observed in close proximity to nNOS-IR or VIP-IR nerve fibers or to eNOS-IR endothelial cells. The distribution of PDEs may indicate a role of these enzymes in the control of the function of the human vagina.