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Effects of diabetes on neurotransmission in rat vaginal smooth muscle

Giraldi, A; Persson, K; Werkström, Viktoria LU ; Alm, Per LU ; Wagner, G and Andersson, K E (2001) In International Journal of Impotence Research 13(2). p.58-66
Abstract
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 EC(50) 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... (More)
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 EC(50) 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Impotence Research
volume
13
issue
2
pages
58 - 66
publisher
Nature Publishing Group
external identifiers
  • pmid:11426340
  • scopus:0034982034
ISSN
1476-5489
DOI
10.1038/sj.ijir.3900648
language
English
LU publication?
yes
id
7966e413-9d39-4783-9bb2-d4a53b184971 (old id 1121345)
date added to LUP
2008-06-27 14:39:48
date last changed
2018-01-07 06:00:30
@article{7966e413-9d39-4783-9bb2-d4a53b184971,
  abstract     = {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 EC(50) value for noradrenaline (NA) was significantly increased (P&lt;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&lt;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&lt;0.001). SNAP and CGRP concentration-dependently inhibited EFS evoked contractions in both NDM and DM preparations. The inhibition was significantly lower (P&lt;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&lt;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.},
  author       = {Giraldi, A and Persson, K and Werkström, Viktoria and Alm, Per and Wagner, G and Andersson, K E},
  issn         = {1476-5489},
  language     = {eng},
  number       = {2},
  pages        = {58--66},
  publisher    = {Nature Publishing Group},
  series       = {International Journal of Impotence Research},
  title        = {Effects of diabetes on neurotransmission in rat vaginal smooth muscle},
  url          = {http://dx.doi.org/10.1038/sj.ijir.3900648},
  volume       = {13},
  year         = {2001},
}