Effect of nitric oxide synthase inhibitors on the temporal coordination of duodenal contractions and pancreatic exocrine secretion in sheep

Abstract

The present study evaluated the role of nitric oxide in the regulation of duodenal motility and pancreatic exocrine secretion in conscious sheep. Intravenous infusions of nitric oxide synthase inhibitors, Nomega-nitro-L-arginine-methyl ester (L-NAME) and Nomega-nitro-L-arginine, induced clusters of duodenal contractions like phase III of migrating motor complexes and simultaneously inhibited flow rate, bicarbonate ion and enzyme outputs of pancreatic juice. The effects of L-NAME were inhibited by simultaneous infusion of L-arginine, but not altered by adrenergic blockade using a combined infusion of phentolamine and propranolol. Inhibition of the pancreatic secretion occurred in coincidence with initiation of the duodenal contractions, while the pancreatic secretion was not inhibited when the premature duodenal contractions were abolished by the L-arginine infusion. The initiation of the cluster of duodenal contractions by L-NAME was not abolished by background infusion of atropine, whereas the amplitude of contractions was significantly inhibited by atropine. These results suggest that intrinsic nitric oxide plays a crucial role in the regulation of duodenal tone and maintenance of continuous secretion by the exocrine pancreas in sheep. These results also implied that inhibition of pancreatic exocrine secretion by the nitric oxide synthase inhibitor is presumably mediated in part through the contractile effect on the duodenum.

Colonic Electrical Stimulation Regulates Colonic Transit Via the Nitrergic Pathway in Rats

“…Accordingly, it is presumed that administration of NOS inhibitor in this study might affect the local level of endogenous NO in the intestinal nerve plexus. On the other hand, it is known that endogenous NO serves as a modulator of the cholinergic postsynaptic neurons which are the final motor nerves innervating the smooth muscles (27). The administration of NOS inhibitor in our study probably led to contraction of the smooth muscle of the descending colon by actions of the cholinergic nerves.…”

“…NO is recognized as an important inhibitory neurotransmitter and plays an important role in the mediation of nonadrenergic, noncholinergic (NANC) relaxation of smooth muscles and in the regulation of gastrointestinal motility (6)(7)(8)(9). The role of endogenous NO synthesized in the gut is often determined by administrating nitric oxide synthase (NOS) inhibitors, such as L-NNA (25)(26)(27)(28). Previous studies have evaluated the role of endogenous NO in the regulation of colonic transit.…”

Role of nitrergic nerves in the regulation of motility of the omasum and abomasum in healthy sheep (Ovis aries)

“…Of course, as there was a difference in recording method between our present study in the omasum and our previous study in the duodenum (Onaga et al 2000); i. e., EMG vs. manometry, we can not completely exclude a Fig. 7 Effect of SNAP application on the bethanechol (BCh)-induced contractions of muscle strips from the ovine omasum.…”

“…In the in vivo experiment, however, intravenous L-NAME infusion did not alter the amplitude of ruminal contractions or EMG activity in the omasum and abomasal antrum. As the doses of L-NAME were in the same range as those in our previous study (Onaga et al 2000) where they evoked clusters of phasic contractions of the ovine duodenum, they seem to be sufficient to inhibit NOS in the digestive tract after intravenous infusion.…”

“…In the second series of experiments, L-NAME was infused (i. v.) in the second 20-min period at doses of 0.3, 1.0, or 3.0 μmol/kg per min. The dose ranges for SNAP and L-NAME were determined on the basis of our previous studies (Onaga et al 2000(Onaga et al , 2001; that is, ranges at which i. v. infusion of SNAP inhibited regular ruminal contractions in sheep, and at which L-NAME infusion induced clusters of contractions similar to premature phase III activity of MMC in the duodenum.…”