ENDOGENOUS NITRIC-OXIDE AS A MEDIATOR OF GASTRIC-MUCOSAL VASODILATATION DURING ACID-SECRETION

被引:136
作者
PIQUE, JM
ESPLUGUES, JV
WHITTLE, BJR
机构
[1] HOSP CLIN BARCELONA,GASTROINTESTINAL UNIT,BARCELONA,SPAIN
[2] UNIV VALENCIA,DEPT PHARMACOL,VALENCIA,SPAIN
[3] WELLCOME RES LABS,DEPT PHARMACOL,BECKENHAM BR3 3BS,KENT,ENGLAND
关键词
D O I
10.1016/0016-5085(92)91797-8
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The role of the endothelium-derived vasodilator, nitric oxide, as a mediator of the increase in gastric mucosal blood flow and as a modulator of the acid secretory response induced by pentagastrin was investigated in the anesthetised rat. Intravenous administration of the selective inhibitor of endogenous nitric oxide synthesis, NG-monomethyl-l-arginine (12.5 and 50 mg/kg), which dose-dependently increased systemic arterial blood pressure, did not affect resting acid output. However, NG-monomethyl-l-arginine significantly reduced resting gastric mucosal blood flow at the higher dose, as determined by hydrogen gas clearance. Infusion of pentagastrin (80 μg kg-1 · h-1) stimulated gastric acid secretion and elevated gastric mucosal blood flow. Pretreatment with NG-monomethyl-l-arginine (12.5 mg/kg IV) did not affect this stimulation of acid output but substantially attenuated (by 65% ± 10%; P < 0.01) the associated increase in gastric mucosal blood flow. Pretreatment with NG-monomethyl-l-arginine (50 mg/kg IV) induced a minor inhibition of pentagastrin-stimulated acid secretion but abolished the increase in gastric mucosal blood flow. When administered during pentagastrin infusion, NG-monomethyl-l-arginine (50 mg/ kg IV) did not affect the acid secretory response but induced a 76% ± 8% inhibition (P < 0.05) of the elevated gastric mucosal blood flow. The effects of NG-monomethyl-l-arginine on blood pressure, acid secretion, and gastric mucosal blood flow were abolished by pretreatment with the precursor for nitric oxide synthesis, l-arginine (300 mg/kg IV). These findings in the rat suggest that endogenous nitric oxide, synthesized from l-arginine, does not directly modulate the acid secretory response induced by pentagastrin but makes a substantial contribution to the mucosal vasodilatation associated with the stimulation of gastric acid secretion. © 1992.
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页码:168 / 174
页数:7
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共 34 条
  • [1] ASHLEY SW, 1984, AM J PHYSIOL, V247, pG339, DOI 10.1152/ajpgi.1984.247.4.G339
  • [2] DRUGGEMAN TW, 1979, GASTROENTEROLOGY, V77, P736
  • [3] ROLE OF ENDOTHELIUM IN RESPONSES OF VASCULAR SMOOTH-MUSCLE
    FURCHGOTT, RF
    [J]. CIRCULATION RESEARCH, 1983, 53 (05) : 557 - 573
  • [4] GERBER JG, 1989, J PHARMACOL EXP THER, V251, P550
  • [5] GASTRIC BLOOD FLOW IN ANAESTHETIZED CATS
    HARPER, AA
    REED, JD
    SMY, JR
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1968, 194 (03): : 795 - &
  • [6] PENTAGASTRIN AND GASTRIC-MUCOSAL BLOOD-FLOW
    HOLMRUTILI, L
    BERGLINDH, T
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1986, 250 (05): : G575 - G580
  • [7] ROLE OF NITRIC-OXIDE IN MAINTAINING VASCULAR INTEGRITY IN ENDOTOXIN-INDUCED ACUTE INTESTINAL DAMAGE IN THE RAT
    HUTCHESON, IR
    WHITTLE, BJR
    BOUGHTONSMITH, NK
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1990, 101 (04) : 815 - 820
  • [8] ENDOTHELIUM-DERIVED RELAXING FACTOR PRODUCED AND RELEASED FROM ARTERY AND VEIN IS NITRIC-OXIDE
    IGNARRO, LJ
    BUGA, GM
    WOOD, KS
    BYRNS, RE
    CHAUDHURI, G
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (24) : 9265 - 9269
  • [9] GASTRIC SECRETION IN RELATION TO MUCOSAL BLOOD FLOW STUDIED BY A CLEARANCE TECHNIC
    JACOBSON, ED
    LINFORD, RH
    GROSSMAN, MI
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1966, 45 (01) : 1 - &
  • [10] JACOBSON ED, 1967, GASTROENTEROLOGY, V51, P466