Blockade of histamine-stimulated alterations in cerebrovascular permeability by the H2-receptor antagonist cimetidine.
Histamine has been shown previously to cause dose-dependent systemic hypotension and concurrent alterations in the permeability of the blood-brain barrier of rats. The purpose of the present study was to determine whether histamine-induced changes in cerebrovascular permeability were mediated by the histamine H2-receptor. Wistar-Kyoto (control) and spontaneously hypertensive rats were pretreated with the histamine H2-receptor antagonist cimetidine (10 mg/kg), followed by saline or histamine (1.25, 2.5 or 5.0 micrograms/kg). Premedication with cimetidine did not block histamine-induced systemic hypotension. The permeability of the blood-brain barrier was measured with 131I-labelled serum albumin (RISA) or with 99mTc-sodium pertechnetate (TcO4-). In both control and spontaneously hypertensive animals, cimetidine prevented histamine-induced changes in the permeability of the blood-brain barrier to either tracer. These findings suggest that the H2-receptor is the prime mediator of histamine-stimulated alterations in cerebrovascular permeability.
Boertje
S B
SB
Department of Biology, Southern University, New Orleans, Louisiana 70126.
Le Beau
D
D
Williams
C
C
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012709:Serum Albumin / Q000378:metabolism; D013670:Sodium Pertechnetate Tc 99m
D006635:Histamine H2 Antagonists; D012709:Serum Albumin; D002927:Cimetidine; D006632:Histamine; D013670:Sodium Pertechnetate Tc 99m