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.