Role of nitric oxide in gastric hyperemia induced by central vagal stimulation

1993 ◽  
Vol 264 (2) ◽  
pp. G280-G284 ◽  
Author(s):  
T. Tanaka ◽  
P. Guth ◽  
Y. Tache
Keyword(s):  
Nitric Oxide ◽  
Acid Secretion ◽  
Vagal Stimulation ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Hydrogen Gas ◽  
Hydrogen Gas Clearance ◽  
Intracisternal Injection ◽  
Stimulation Of

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, on the vagal cholinergic increase in gastric mucosal blood flow (GMBF) and acid secretion induced by intracisternal injection of the thyrotropin-releasing hormone (TRH) analogue, RX 77368, were studied. GMBF and acid secretion were measured simultaneously by the hydrogen gas clearance technique and titration of gastric perfusate in urethan-anesthetized rats. RX 77368 (30 ng) injected intracisternally stimulated gastric acid secretion and GMBF for 90 and 180 min respectively. GMBF was increased from basal 63 +/- 4 to 166 +/- 14 ml.min-1.100 g-1 at 60 min postinjection. L-NAME (3 mg/kg) injected intravenously 15 min before RX 77368 completely prevented the increase in GMBF induced by the TRH analogue, whereas the acid response was not modified. The effect of L-NAME was reversed by L-arginine but not by the stereoisomer D-arginine. These results show that the increase in GMBF, but not the stimulation of acid secretion, induced by central vagal activation is mediated through a product of L-arginine-NO pathway.

Peripheral mediators involved in gastric hyperemia to vagal activation by central TRH analog in rats

1998 ◽  
Vol 274 (1) ◽  
pp. G170-G177 ◽  
Author(s):  
Ágnes Király ◽  
Gábor Sütö ◽  
Paul H. Guth ◽  
Yvette Taché
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Methyl Ester ◽  
Gastric Acid ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Hydrogen Gas ◽  
Hydrogen Gas Clearance ◽  
Afferent Fibers ◽  
Intracisternal Injection

Mechanisms mediating the increase in gastric mucosal blood flow (GMBF) induced by the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracisternally at a gastric acid secretory dose (30 ng) were investigated using hydrogen gas clearance in urethan-anesthetized rats. The histamine H1 receptor antagonist pyrilamine (intravenously), capsaicin (subcutaneously, −10 days), and N G-nitro-l-arginine methyl ester (l-NAME, intracisternally) failed to impair the 150% rise in GMBF induced by intracisternal injection of RX-77368. By contrast, atropine (subcutaneously) and N G-monomethyl-l-arginine (intravenously) completely inhibited the increase in GMBF evoked by intracisternal RX-77368. l-NAME (intravenously) blocked the intracisternal RX-77368-induced increase in GMBF in capsaicin-pretreated rats, and thel-NAME effect was reversed by intravenous l- but notd-arginine. These findings indicate that vagal efferent activation induced by TRH analog injected intracisternally at a gastric acid secretory dose increases GMBF through atropine-sensitive mechanisms stimulatingl-arginine-nitric oxide pathways, whereas H1 receptors and capsaicin-sensitive afferent fibers do not play a role.

Mechanisms mediating gastric hyperemic and acid responses to central TRH analog at a cytoprotective dose

1997 ◽  
Vol 273 (1) ◽  
pp. G31-G38
Author(s):  
A. Kiraly ◽  
G. Suto ◽  
P. H. Guth ◽  
Y. Tache
Keyword(s):  
Acid Secretion ◽  
Vagal Stimulation ◽  
Mucosal Blood Flow ◽  
Hydrogen Gas ◽  
Inhibitory Influence ◽  
Hydrogen Gas Clearance ◽  
Afferent Fibers ◽  
Calcitonin Gene ◽  
Before And After ◽  
Underlying Mechanisms

Gastric hyperemic and acid responses to the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracisternally at a cytoprotective dose were investigated, as well as the underlying mechanisms of the responses. Gastric acid secretion (GAS), mucosal blood flow (GMBF; measured by the hydrogen gas clearance technique), and mucosal vascular resistance (GMVR) and mean arterial pressure (MAP) were assessed simultaneously for 30 min before and after RX-77368 (1.5 ng) administration in urethan-anesthetized rats. RX-77368 increased GMBF from 46.8 +/- 5.3 to 100.6 +/- 20.9 ml.min-1.100 g-1 and MAP from 70.3 +/- 2.1 to 84.3 +/- 5.9 mmHg and decreased GMVR from 1.50 +/- 0.33 to 0.84 +/- 0.08 mmHg.ml-1.min.100 g, whereas GAS was not significantly altered (1.8 +/- 0.4 vs. 4.7 +/- 1.7 mumol/30 min) in vehicle-pretreated rats. The GMBF, MAP, and GMVR responses to RX-77368 were not modified by indomethacin (5 mg/kg ip), whereas GAS was increased. In rats pretreated with capsaicin (125 mg/kg sc) or calcitonin gene-related peptide (CGRP) antagonist hCGRP-(8-37), intracisternal RX-77368 did not increase GMBF or decrease GMVR but did stimulate GAS. These data show that vagal stimulation by the TRH analog RX-77368 injected intracisternally at a nonacid secretory dose increases GMBF. Gastric hyperemia is mediated by CGRP contained in capsaicin-sensitive afferent fibers, whereas acid secretion is under the inhibitory influence of prostaglandins and CGRP.

Central vagal activation by TRH induces gastric hyperemia: role of CGRP in capsaicin-sensitive afferents in rats

1994 ◽  
Vol 267 (6) ◽  
pp. G1041-G1049 ◽  
Author(s):  
A. Kiraly ◽  
G. Suto ◽  
E. H. Livingston ◽  
P. H. Guth ◽  
S. St Pierre ◽  
...  
Keyword(s):  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Hydrogen Gas ◽  
Hydrogen Gas Clearance ◽  
Afferent Fibers ◽  
Substance P Antagonist ◽  
Calcitonin Gene ◽  
Hyperemic Response ◽  
Cgrp Antagonist

The role of calcitonin gene-related peptide (CGRP) in the vagal cholinergic-mediated increase in gastric mucosal blood flow (GMBF) induced by the stable thyrotropin-releasing hormone (TRH) analogue RX-77368 injected intracisternally (ic, 30 ng) was investigated in urethan-anesthetized rats using the hydrogen gas clearance technique. alpha-CGRP (14 micrograms.kg-1.h-1) or bethanechol (150 micrograms.kg-1.h-1) infused close intra-arterially to the stomach or RX-77368 injected intracisternally increased GMBF by 76, 102, and 131%, respectively, 30 min after administration. The CGRP antagonist, human CGRP-(8-37) [hCGRP-(8-37)], injected intravenously (15 micrograms/kg bolus and 3 micrograms.kg-1.h-1) inhibited by 100, 97, and 73% the gastric hyperemic response to alpha-CGRP, TRH analogue, and bethanechol, respectively, whereas the substance P antagonist CP-96,345 (3 mg/kg iv) had no effect. In capsaicin-pretreated rats, hCGRP-(8-37) no longer blocked the increase in GMBF induced by intracisternal RX-77368. These results suggest that the gastric hyperemic response to central vagal activation induced by intracisternal TRH analogue at 30 ng is mediated by local effector function of capsaicin-sensitive afferent fibers releasing CGRP.

Dissociated effects of corticotropin-releasing factor on acid secretion and blood flow

1989 ◽  
Vol 256 (2) ◽  
pp. G412-G417
Author(s):  
G. Thiefin ◽  
F. W. Leung ◽  
Y. Tache ◽  
P. H. Guth
Keyword(s):  
Blood Flow ◽  
Acid Secretion ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Systemic Blood Pressure ◽  
Hydrogen Gas ◽  
Corticotropin Releasing Factor ◽  
Hydrogen Gas Clearance ◽  
Systemic Hypotension ◽  
Antisecretory Effect

Peripherally administered corticotropin-releasing factor (CRF) inhibits gastric acid secretion in the rat via unknown mechanisms. Because intravenous CRF can produce marked systemic hypotension, the hypothesis that its antisecretory effect is due to a reduction in gastric mucosal blood flow (MBF) was tested. Corpus MBF was measured by hydrogen gas clearance in fasted, urethan-anesthetized rats. CRF (15 nmol.kg-1.h-1 iv) had no significant effect on MBF but significantly decreased systemic blood pressure (BP) by 21.8 +/- 3.4%. This dose of CRF significantly decreased acid secretion stimulated by 40 micrograms.kg-1.h-1 pentagastrin iv but did not decrease MBF despite a 30.3 +/- 2.3% decrease in BP. To avoid the confounding effect of systemic hypotension on MBF, close gastric intra-arterial infusions were performed. CRF (1.7 nmol/h ia) had no effect on BP and did not increase MBF. CRF (3.4 nmol/h ia) slightly decreased BP without modifying MBF. In contrast, histamine (200 micrograms/h ia) significantly increased MBF by 58 +/- 11%. We conclude that 1) the peripheral antisecretory effect of CRF is not related to a decrease in MBF, 2) the maintenance of MBF during CRF-induced hypotension is not due to a direct vasodilator effect of CRF on the gastric microvasculature.

Gastric mucosal hyperemia due to acid backdiffusion depends on splanchnic nerve activity

1992 ◽  
Vol 262 (3) ◽  
pp. G505-G509 ◽  
Author(s):  
P. Holzer ◽  
I. T. Lippe
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Hydrogen Gas ◽  
Mucosal Barrier ◽  
Neural Pathways ◽  
Hydrogen Gas Clearance ◽  
Celiac Ganglion ◽  
Arterial Blood ◽  
Splanchnic Nerves

Acid backdiffusion through a disrupted gastric mucosal barrier leads to an increase in gastric mucosal blood flow (MBF). This response involves afferent neurons that pass through the celiac ganglion. The present study examined the neural pathways that underlie the rise in MBF caused by gastric perfusion with 15% ethanol in 0.15 N HCl. MBF was measured by the hydrogen gas clearance technique in urethan-anesthetized rats. Mucosal hyperemia due to acid backdiffusion was not changed by acute bilateral subdiaphragmatic vagotomy but was blocked by acute removal of the celiac-superior mesenteric ganglion complex or acute bilateral transection of the greater splanchnic nerves. Hexamethonium (85 mumol/kg iv) also attenuated the rise in MBF due to acid backdiffusion, whereas guanethidine (0.225 mmol/kg sc) had no effect. None of the procedures and drug treatments altered basal MBF to a significant extent. Transection of the splanchnic nerves, hexamethonium, and guanethidine lowered mean arterial blood pressure, but hypotension as such did not significantly influence the hyperemic response under study. Taken together, the previous and present data indicate that the rise in MBF caused by acid backdiffusion depends on the integrity of afferent and efferent neural pathways that run in the splanchnic nerves and through the celiac ganglion. The efferent pathway involves ganglionic transmission through nicotinic acetylcholine receptors but is independent of noradrenergic neurons.

Cholecystokinin secretagogue-induced gastroprotection: role of nitric oxide and blood flow

2003 ◽  
Vol 284 (3) ◽  
pp. G399-G410 ◽  
Author(s):  
Sonlee D. West ◽  
Kenneth S. Helmer ◽  
Lily K. Chang ◽  
Yan Cui ◽  
George H. Greeley ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Gastric Injury ◽  
Protective Mechanism ◽  
Adaptive Cytoprotection ◽  
Mucosal Defense ◽  
Calcium Dependent

This study was done to examine the role of CCK in gastric mucosal defense and to assess the gastroprotective roles of nitric oxide and blood flow. In rats, the CCK secretagogues oleate and soybean trypsin inhibitor augmented gastric mucosal blood flow and prevented gastric injury from luminal irritants. Type A CCK receptor blockade negated CCK secretagogue-induced gastroprotection and exacerbated gastric injury from bile and ethanol but did not block adaptive cytoprotection. CCK secretagogue-induced gastroprotection and hyperemia were negated by nonselective nitric oxide synthase (NOS) inhibition ( N G-nitro-l-arginine methyl ester) but not by selective inducible NOS inhibition (aminoguanidine). Gastric mucosal calcium-dependent NOS activity, but not calcium-independent NOS activity, was increased following CCK and CCK secretagogues. The release of endogenous CCK plays a role in the intrinsic gastric mucosal defense system against injury from luminal irritants. The protective mechanism appears to involve increased production of nitric oxide from primarily the constitutive isoforms of NOS and a resultant increase in blood flow.

Capsaicin-sensitive afferent fibers contribute to gastric mucosal blood flow response to electrical vagal stimulation

1990 ◽  
Vol 259 (6) ◽  
pp. G1037-G1043 ◽  
Author(s):  
G. Thiefin ◽  
H. E. Raybould ◽  
F. W. Leung ◽  
Y. Tache ◽  
P. H. Guth
Keyword(s):  
Blood Flow ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Vagal Stimulation ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Vascular Response ◽  
Antidromic Activation ◽  
Afferent Fibers

Electrical stimulation of the peripheral vagus produces a noncholinergic increase in gastric mucosal blood flow (GMBF) via unknown mechanisms. The purpose of this study was 1) to investigate whether a portion of the increase in GMBF during prolonged electrical vagal stimulation involves a mechanism separate from augmented acid secretion and 2) to determine whether antidromic activation of afferent fibers contributes to the vascular or secretory responses to electrical vagal stimulation. Electrical vagal stimulation (40 V, 6 Hz, 2 ms) applied for 30 min to the distal cut end of the subdiaphragmatic ventral vagus significantly increased gastric acid secretion and GMBF measured by hydrogen gas clearance. Atropine (0.15 mg/kg iv) or omeprazole (10 mumol/kg iv) completely abolished the secretory response to electrical vagal stimulation, while a significant increase in GMBF remained. Pretreatment with perineural application of the sensory neurotoxin capsaicin to both cervical vagi significantly reduced by 48% the increase in GMBF but not gastric acid secretion; atropine completely abolished the remaining vascular response in capsaicin-treated rats. These results suggest that prolonged electrical vagal stimulation induces a sustained increase in GMBF partially independent of augmented acid secretion and that the noncholinergic portion of the vascular response is mediated by capsaicin-sensitive vagal afferent fibers.

Gastric mucosal blood flow response to stress in streptozotocin diabetic rats: Regulatory role of nitric oxide

1997 ◽  
Vol 32 (6) ◽  
pp. 726-733 ◽  
Author(s):  
Hitoshi Suzuki ◽  
Tooru Shimosegawa ◽  
Akihiko Satoh ◽  
Kenji Kimura ◽  
Shuichi Ohara ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Diabetic Rats ◽  
Blood Flow Response ◽  
Flow Response ◽  
Response To Stress ◽  
Streptozotocin Diabetic Rats

Dissociated effects of somatostatin on gastric acid secretion and mucosal blood flow

1985 ◽  
Vol 248 (3) ◽  
pp. G337-G341
Author(s):  
F. W. Leung ◽  
P. H. Guth
Keyword(s):  
Blood Flow ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Acid Output ◽  
Mucosal Blood Flow ◽  
Hydrogen Gas ◽  
Gastric Acid Output ◽  
Hydrogen Gas Clearance ◽  
Blood Flows

Somatostatin has been reported to control upper gastrointestinal hemorrhage, prevent restraint stress-induced gastric ulcerations, and inhibit gastric acid secretion. In this study we examined the effect of somatostatin on basal and pentagastrin-stimulated gastric acid output and mucosal blood flow. Antral and corpus mucosal blood flows were measured by hydrogen gas clearance in fasted, anesthetized rats. Acid output was determined by a continuous gastric perfusion technique. In the basal study somatostatin in doses of 8, 16, and 32 micrograms . kg-1 . h-1 was infused intravenously in separate groups of animals. In the pentagastrin stimulation study somatostatin (16 micrograms . kg-1 . h-1) was infused after gastric acid output was stimulated to plateau by intravenous pentagastrin (19.8 micrograms . kg-1 . h-1). The results showed that somatostatin had no effect on basal corpus or antral mucosal blood flow. During pentagastrin stimulation somatostatin decreased acid secretion but increased corpus mucosal blood flow. We speculate that this increase in blood flow may not be a direct effect as basal corpus or antral mucosal blood flow was unaffected by somatostatin.

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