Effects of nitric oxide inhibition on duodenal function in rat: involvement of neural mechanisms.
This study examines the integrative response of several duodenal functions to nitric oxide synthase inhibition. Effects of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) were studied in anesthetized rats, using in situ duodenal perfusion. L-NAME increased bicarbonate secretion, permeability, and fluid secretion and induced motility. Injection of L-arginine abolished L-NAME-induced motility and lowered the secretion of bicarbonate and fluid. Pretreatment with the nicotinic receptor antagonist hexamethonium prevented the rise in bicarbonate secretion and motility in response to L-NAME but did not affect the increase in mucosal permeability. Atropine diminished the L-NAME-induced increases in permeability, motility, and fluid secretion. The adrenolytic drug guanethidine did not alter the responses to the inhibitor. These results suggest that nitric oxide inhibits duodenal motility and bicarbonate secretion by suppressing a stimulatory, nicotinic receptor-dependent, neural mechanism. The L-NAME-induced contractions involve both a cholinergic, atropine-sensitive pathway and nonadrenergic, noncholinergic neural transmission. Muscarinic receptors also mediate part of the L-NAME-induced increases in mucosal permeability and fluid secretion.
Hällgren
A
A
Department of Physiology and Medical Biophysics, Uppsala University, Sweden.
Flemström
G
G
Sababi
M
M
Nylander
O
O
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D006145:Guanethidine / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009424:Nervous System Physiological Phenomena; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D009569:Nitric Oxide; D018738:Hexamethonium; D001285:Atropine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D006145:Guanethidine