TITLE

INVESTIGATING THE ROLE FOR NORADRENALINE IN NEUROGENIC RESPONSES OF THE SHEEP INTERNAL ANAL SPHINCTER

AUTHOR(S)
Acheson, A.G.; Scholefield, J.H.; Wilson, V.G.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA29
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Introduction: Nitric oxide (NO) is the principal inhibitory neurotransmitter in the internal anal sphincter (lAS) of humans and sheep with noradrenaline (NA) responsible for causing neurogenic contractions via cc adrenoceptors following inhibition of NO synthase. Previous work using isolated lAS tissue from sheep has surprisingly shown that phentolamine, an cc adrenoceptor antagonist, fails to enhance neurogenic relaxations under control conditions. This study aims to further investigate the nature oF neurogenic responses of the sheep lAS. Methods: Using an established sheep lAS model, strips of internal sphincter were placed in isolated organ baths. The neurogenic responses to 1 Hz and 10 Hz stimulation (300 mA pulse strength, 0.3 ms pulse width, 30 s every 180 s) in the presence and absence of 3 µM phentolamine were tested. Results: There was no significant difference in the magnitude of the neurogenic relaxations observed following stimulation at 1 Hz or 10 Hz and the addition of 3 pM phentolamine failed to enhance these responses at either frequency. The time taken for the neurogenic relaxations to return to 50% of the initial tone was significantly longer with 1 Hz (34.6 ± 0.6 sec) compared with 10 Hz (25.8 ± 1.9 sec, n = 24, p < 0.05). Phentolamine had no effect on the duration of these responses at 1 Hz but significantly prolonged the responses at 10 Hz (32.1 ± 1.5 sec, n = 24, p < 0.05). Conclusion: Based on the effects of phentolamine, NA is released at 10 Hz but not 1 Hz. NA does not alter the magnitude of the neurogenic relaxations, but limits the time course of the response. Phentolamine, an cc adrenoceptor antagonist, increased the time course of the neurogenic relaxations and therefore preserved the effects of neuronal NO. These Findings raise the possibility that topical cc adrenoceptor antagonists may be useful, either with or without a direct acting relaxant, in instances of excessive adrenergic tone (eg anal fissures).
ACCESSION #
9747456

 

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