Effect of histamine on haemorrhagic mucosal lesions is related to vascular permeability in rats: studies with histamine, H1-, H2- and H3-agonists and bradykinin.
OBJECTIVE
To test the hypothesis that an early increase in vascular permeability is correlated with later gastric mucosal protection in the rat.


METHODS
Histamine, its agonists (H1, H2, H3) and bradykinin, were either given subcutaneously or intragastrically before the intragastric administration of ethanol. The extravasation of intravenously injected 99mTc-glucoheptonate into the gastric wall and into the gastric contents was used as an indicator of increased permeability. Gastric haemorrhagic lesions where measured by computerized planimetry and ethanol absorption was determined by an ACA Clinical Analyzer.


RESULTS
Histamine and bradykinin increased vascular permeability in the glandular stomach and provided significant gastroprotection, similar to H1-, H2- and H3-agonists, against ethanol-induced gastric haemorrhagic lesions. This gastroprotection was accompanied by low blood levels of ethanol, probably indicating decreased ethanol absorption and the creation of a histodilutional barrier in the stomach by histamine.


CONCLUSIONS
These data indicate that an increase in vascular permeability dissipates the concentration, and may delay the absorption, of ethanol in gastric mucosa by creating a perivascular histodilutional barrier. Vascular injury, which is an early pathogenetic factor in the development of ethanol-induced gastric haemorrhagic erosions, may thus be prevented.
Palitzsch
K D
KD
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Morales
R E
RE
Kronauge
J F
JF
Bynum
T E
TE
Szabo
S
S
D000042:Absorption; D000818:Animals; D001621:Betahistine / Q000008:administration & dosage / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D017259:Dimaprit / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000503:physiopathology*; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D017442:Histamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007441:Intubation, Gastrointestinal; D008761:Methylhistamines / Q000008:administration & dosage / Q000494:pharmacology; D015609:Organotechnetium Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D013272:Stomach Diseases / Q000503:physiopathology*; D013400:Sugar Acids
D017442:Histamine Agonists; D008761:Methylhistamines; D015609:Organotechnetium Compounds; D013400:Sugar Acids; D000431:Ethanol; C069357:alpha-methylhistamine; D006632:Histamine; C100014:technetium Tc 99m gluceptate; D001920:Bradykinin; D001621:Betahistine; D017259:Dimaprit