Production and antagonism of cutaneous vascular permeability in the guinea pig in response to histamine, leukotrienes and A23187.
The method of Katayama et al. (Microbiol. Immunol. 22:89-101, 1978) for assessing cutaneous vascular permeability was modified and used to evaluate responses of the dermal vasculature to histamine, leukotriene (LT)C4, LTD4 and the ionophore A23187. These agonists were given intradermally, whereas antagonists and other types of inhibitors were administered i.v. Histamine was shown to cause vascular leakage via an H1 receptor. No evidence for H2 receptor activation or involvement of cyclooxygenase products was found. The results also suggested that a portion of the response to histamine was due to the liberation of LTD4. LTC4 produced a mixed response comprised of vasoconstriction and increased vascular permeability, the latter possibly due to its conversion to LTD4. FPL 55712 antagonized LTD4-induced permeability in a dose-dependent manner, whereas indomethacin had no effect. Neither pyrilamine nor FPL 55712 reduced the response to A23187. A dose of indomethacin that did not affect the response to A23187 when given alone markedly reduced the ability of ionophore to cause vascular leakage when combined with either pyrilamine or FPL 55712. Thus, histamine and LTD4, in combination with one or more of the cyclooxygenase products, may be involved in A23187-induced cutaneous vascular permeability. Finally, two calcium channel blocking agents, nifedipine and diltiazem, did not block the vascular leakage caused by A23187.
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000008:administration & dosage / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007271:Injections, Intradermal; D008297:Male; D011738:Pyrilamine / Q000494:pharmacology; D011968:Receptors, Histamine / Q000378:metabolism; D013189:SRS-A / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply*
D002867:Chromones; D011968:Receptors, Histamine; D013189:SRS-A; D000001:Calcimycin; D006632:Histamine; C006312:FPL 55712; D011738:Pyrilamine; D001920:Bradykinin; D007213:Indomethacin