Homocysteine is a significant but modifiable risk factor for vascular
diseases. As gastrointestinal smooth musculature is similar to blood vessel
muscles, we investigated how elevated homocysteine levels affect nitric
oxide-mediated neurotransmission in the gut. There is accumulated evidence
that a dysfunction of NO neurons in the myenteric plexus may cause various
diseases in the gastrointestinal tract such as achalasia, diabetic
gastroparesis and infantile hypertrophic pyloric stenosis. In the present
study, we aimed to assess the effects of homocysteine on NO-mediated
responses in vitro, and to examine the effects of DL-homocysteine thiolactone
on the spontaneous motility of rat duodenum and nitrergic neurotransmission.
DL-homocysteine thiolactone concentration of 10 μmol/L leads to the immediate
increase in tone, amplitude and frequency of spontaneous movements in
isolated rat duodenum. L-NAME (30 μmol/L) leads to an increase in basal tone,
amplitude and frequency of spontaneous contractions. The relaxations induced
by EFS were significantly reduced in duodenal segments incubated in
DL-homocysteine thiolactone compared with the control group. EFS-induced
relaxations were inhibited by L-NAME in both experimental and control groups.
These results suggest that a high level of homocysteine causes an important
impairment of non-adrenergic non-cholinergic innervation of the rat duodenum.
[Projekat Ministarstva nauke Republike Srbije, br. 175043
