Acetylcholine released from guinea‐pig submucosal neurones dilates arterioles by releasing nitric oxide from endothelium.

Abstract

SUMMARY1. The role of the endothelium as an effector of the neurogenic cholinergic vasodilatation in submucosal arterioles of the guinea-pig ileum was investigated by measuring changes in arteriolar diameter in response to exogenous application of muscarine or electrical stimulation of the submucosal ganglia.2. NG-Monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthesis, competitively inhibited the vasodilatation produced by muscarine in arterioles which had been preconstricted with the prostaglandin analogue U46619. L-Arginine (10 mM), but not D-arginine (10 mM), prevented the inhibition by L-NMMA.3. Neither tetrodotoxin (TTX, 1 IUM), nor the cyclo-oxygenase inhibitor, indomethacin (10 /tM), altered the muscarinic vasodilatation or the inhibitory effect of L-NMMA.4. Sodium nitroprusside (SNP), an activator of the soluble guanylate cyclase, dilated the arterioles in a concentration-dependent manner. This vasodilatation was unaffected by L-NMMA but was abolished by the guanylate cyclase inhibitor, methylene blue (10 tM). In addition, methylene blue antagonized the muscarinic vasodilatation to a similar degree as did L-NMMA.5. The vasodilatation produced by ganglionic stimulation (10 Hz, 10 s) was blocked by TTX and the muscarinic receptor antagonist, 4-diphenylacetoxy-Nmethyl-piperidine methiodide (4-DAMP, 1 ,UM). The neurally evoked vasodilatation was inhibited by 70 % in the presence of L-NMMA; this inhibition was prevented by L-arginine. Methylene blue inhibited the neurogenic vasodilatation to the same extent as did L-NMMA.6. These results show that arteriolar vasodilatation by muscarine is mediated mainly through the release of NO formed from L-arginine; the origin of the L-arginine appears to be the endothelium. These results also demonstrate that acetylcholine released from submucosal nerves onto submucosal blood vessels reaches the endothelium to cause the release of NO formed from L-arginine; the endothelialderived NO dilates the arteriole.MS 9832

Requirement for endothelium‐derived nitric oxide in vasodilatation produced by stimulation of cholinergic nerves in rat hindquarters

“…Recent attempts to determine whether NO does mediate cholinergic neurogenic vasodilatation have involved the use of NO synthase inhibitors such as NG-nitro-L-arginine (L-NOARG) and its methyl ester (L-NAME) as well as NG_ monomethyl-L-arginine (L-NMMA) (Broten et al, 1992;McMahon et al, 1992;Andriantsitohaina & Suprenant, 1992;Loke et al, 1994). These studies all concluded that NO mediates cholinergic neurogenic dilatation although the results of the two studies using L-NAME (McMahon et al, 1992;Broten et al, 1992) must be viewed with some caution due to the subsequent report that L-NAME possesses muscarinic receptor antagonist activity (Buxton et al, 1993).…”

Metabotropic Signal Transduction for Bradykinin in Submucosal Neurons of Guinea Pig Small Intestine

“…Secretomotor neurons are the final common motor pathways from the integrative networks of the enteric nervous system to the intestinal secretory glands (i.e., crypts of Lieberkü hn). They transmit the signals for autonomic minute-to-minute regulation of mucosal secretion and liquidity of the intestinal contents in concert with submucosal vasodilation and increased blood flow in support of stimulated secretion (Andriantsitohaina and Surprenant, 1992;Cooke, 2000). Enhanced mucosal secretion, after elevation of excitability in secretomotor neurons, increases the liquidity of the luminal contents and might lead to neurogenic secretory diarrhea.…”

Neuropathophysiology of functional gastrointestinal disorders

“…Active firing of secretomotor neurons releases acetylcholine simultaneously at neuroepithelial and neurovascular junctions. Acetylcholine acts at the blood vessels level to release nitric oxide from the endothelium, which in turn dilates the vessels and increases blood flow [42] . Secretomotor neurons have receptors that receive excitatory and inhibitory synaptic input from other neurons in the integrative circuitry of the ENS and from sympathetic postganglionic neurons (Figure 3) [43][44][45] .…”

“…Collateral projections from the secretomotor axons innervate submucosal arterioles (Figure 3). Collateral innervation of the blood vessels links secretomotor activity in the glands to submucosal blood flow [42] . Active firing of secretomotor neurons releases acetylcholine simultaneously at neuroepithelial and neurovascular junctions.…”