Histamine-induced microvascular permeability increases in hamster skin: a response predominantly mediated by H2-receptors.
The pharmacology of histamine-induced increases in cutaneous microvascular permeability was investigated in the hamster by examining the effects of cimetidine and pyrilamine on the increase in microvascular permeability evoked by graded doses of intradermally-injected histamine, and comparing the cutaneous microvascular permeability responses to graded doses of impromidine (0.1-100 micrograms), dimaprit (1-100 micrograms) and beta-histine (0.1-100 micrograms). Pretreatment with pyrilamine (0.1 mg/kg i.v. bolus injection) did not reduce the increase in microvascular permeability produced by any dose of histamine. In contrast, cimetidine (0.5 mg/kg/min i.v. infusion) significantly inhibited the microvascular permeability responses to 10 and 100 micrograms histamine. Although neither cimetidine nor pyrilamine significantly altered the microvascular permeability response to 0.1 and 1 micrograms histamine, inhibition was afforded by a cimetidine-pyrilamine combination. These results suggest a predominantly H2-receptor mediated phenomenon with a minor H1-receptor mediated component. Studies with the H2-receptor agonists impromidine and dimaprit and the H1-receptor agonist beta-histine provide further support for this contention. Dimaprit and impromidine caused a dose-dependent increase in cutaneous microvascular permeability, but betahistine produced only a relatively modest response. In other laboratory species, increased cutaneous microvascular permeability appears to be mediated solely by H1-receptors. Therefore, the hamster skin appears unique with respect to the pronounced H2-receptor involvement in histamine-induced microvascular permeability changes.
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008647:Mesocricetus; D011738:Pyrilamine / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000502:physiology*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects
D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; D011738:Pyrilamine