Histamine involvement in the local and systemic microvascular effects produced by intradermal substance P.
The cutaneous microvascular changes produced by intradermal substance P were quantitatively evaluated in both substance P-injected and contralateral, saline-injected guinea pig ears. Substance P evoked a dose-dependent increase in cutaneous microvascular permeability in both treated and untreated ears which was reduced, but not abolished, by a mepyramine-cimetidine combination. This indicates that the local effect of substance P on microvascular permeability and the effect on the contralateral ear (presumably the result of systemic substance P absorption) are both partially mediated by histamine. A cutaneous vasodilator response was also observed in substance P treated and contralateral ears, but a bell-shaped dose-response relationship was apparent. Unlike microvascular permeability, pretreatment with mepyramine and cimetidine failed to consistently attenuate the vasodilator response to substance P. Thus, a direct cutaneous vasodilator effect appears to predominate in both substance P-injected and saline-injected ears.
Woodward
D F
DF
Owen
D A
DA
Pipkin
M A
MA
Ledgard
S E
SE
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D002927:Cimetidine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004423:Ear; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage; D007271:Injections, Intradermal; D008297:Male; D011738:Pyrilamine / Q000008:administration & dosage; D011968:Receptors, Histamine / Q000187:drug effects / Q000502:physiology*; D012867:Skin / Q000098:blood supply*; D013373:Substance P / Q000008:administration & dosage*
D011968:Receptors, Histamine; D013373:Substance P; D002927:Cimetidine; D006632:Histamine; D011738:Pyrilamine