Histamine involvement in the local and systemic microvascular effects produced by intradermal substance P

Abstract

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.

Peptidergic sensory neurons in the control of vascular functions: Mechanisms and significance in the cutaneous and splanchnic vascular beds

“…Blood flow in the femoral artery (Hallberg and Pernow 1975) and skin of the dog (Burcher et al 1977) and rat ) is also augmented by intravenous administration of SP. Intradermal injection of SP enhances cutaneous blood flow in the guinea pig (Woodward et al 1985) but fails to change it in the rat dorsal skin Williams 1988, 1989). However, when perfused over a blister base in the rat footpad skin, SP causes hyperaemia , as does topical administration of SP to the hamster cheek pouch (Raud et at.…”

“…When injected into the skin of guinea pigs (Woodward et al 1985;Iwamoto and Nadel 1989), mice (Yano et al 1989), rats (Chahl 1979;Gamse and Saria 1985b;Devillier et al 1986a;Maggi et al 1987a;Yonehara et al 1987;Williams 1988, 1989; D e v o r e t al. 1989) or humans (H~igermark et al 1978;Carpenter and Lynn 1981;Anand et al 1983;Foreman et al 1983;Jorizzo et al 1983;Piotrowski and Foreman 1985;Devillier et al t986a;Fuller et al 1987;Wallengren and H~kanson 1987;Williams 1988, 1989;Pedersen-Bjergaard et al 1989Iwamoto et al 1990;Heyer et al 1991), tachykinins induce plasma protein leakage and local oedema (weal).…”

“…The histamine-dependent component of the exudative response to SP (H~germark et al. 1978;Chahl 1979;Lembeck and Holzer 1979;Foreman et al 1983;Jorizzo et al 1983;Woodward et al 1985;Fuller et at. 1987; Wallengren and H~kan-son 1987; Brain and Williams 1989; Khalil and Helme 1989b) and…”

“…4. Both the vasodilator (Lembeck and Holzer 1979; and exudative (H~igermark et al+ 1978;Chahl 1979;Lembeck and Holzer 1979;Foreman et al 1983;Jorizzo et al 1983;Woodward et al 1985;Fuller et al 1987;Wallengren and H~kanson 1987;Brain and Williams 1989;Khalil and Helme 1989b) effects of SP can in part be inhibited by histamine antagonists, sometimes in combination with methysergide (Chahl 1979). In the guinea pig skin, histamine appears to play a more important role in the exudative effects of SP than in the vasodilator effects of the peptide (Woodword et al.…”