¹Division of Sexual Physiology, Rigshospitalet, Department of Physiology, University of Copenhagen, Copenhagen, Denmark

²Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden

³Department of Pathology, Lund University Hospital, Lund, Sweden

Correspondence to: A Giraldi, Division of Sexual Physiology, Rigshospitalet, Blegdamsvej 9, Div. 7702, 2100 Copenhagen, Denmark. Tel: +45 35 45 71 31; Fax: +45 35 35 16 05. E-mail: giraldi@RH.dk

This paper is co-winner of the Ginestie Prize, awarded at the 9th World Meeting on Impotence Research, Perth, Australia 26 - 30 November 2000.

The aim of this work was to characterize the effect of experimental diabetes on neurotransmission in rat vagina. Female Sprague-Dawley rats were divided into two groups: non-diabetic controls (NDM, n=38) and diabetics (DM, n=38). DM was produced by intraperitoneal injection of streptozotocin. Eight weeks later the animals were killed, the distal part of the vagina was removed, and smooth muscle strips were prepared for functional organ bath experiments and for measurement of nitric oxide synthase (NOS) activity. In DM preparations, the EC₅₀ value for noradrenaline (NA) was significantly increased (P<0.05) and the maximal contractile response decreased (P=0.001). In preparations precontracted with NA, the NO donor SNAP and calcitonin gene-related peptide (CGRP) caused concentration-dependent relaxations, which were significantly decreased (P<0.001) in the DM group. Electrical stimulation of nerves (EFS) caused frequency-dependent contractions, which were significantly lower in DM than in NDM strips (P<0.001). SNAP and CGRP concentration-dependently inhibited EFS evoked contractions in both NDM and DM preparations. The inhibition was significantly lower (P<0.05) in the DM group. In NDM preparations precontracted with NA, EFS evoked frequency-dependent relaxations; such relaxations were inhibited or reduced in DM. Treatment with the NOS inhibitor, L-NOARG 0.1 mM, abolished relaxations in all preparations or produced contraction in DM preparations. Calcium-dependent NOS activity was not significantly different in the DM and NDM groups. However, the DM animals showed a small but significant increase in calcium-independent NOS-activity (P<0.05). Diabetes interferes with adrenergic-, cholinergic- and NANC-neurotransmitter mechanisms in the smooth muscle of the rat vagina. The changes in the nitrergic neurotransmission are not due to reduction in NOS-activity, but seem to be due to interference with later steps in the L-arginine/NO/guanylate cyclase/cGMP system.

International Journal of Impotence Research (2001) 13, 58-66

vagina; smooth muscle; female sexual dysfunction; diabetes; rat