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

Nitric oxide mediates the amplification by interleukin-1β of neurogenic vasodilatation in the rat skin

“…The residual vasodilatation seen in capsaicin-pretreated rats is likely to be a reaction to the injection per se, since it was not higher than the vasodilatation caused by intraplantar injection of saline alone. These findings are consistent with the notion that the capsaicin-induced rise of cutaneous blood flow is mediated by stimulation of fine afferent nerve fibres (Holzer, 1992) and release of the vasodilator transmitter CGRP (Hughes and Brain, 1991;Brain et al, 1993). Hence, the absence of any effect of interleukin-lß in capsaicin-pretreated rats implies that the cytokine augments the neurogenic component in the vasodilator response to capsaicin by sensitizing afferent nerve fibres to noxious stimuli.…”

“…Firstly, NO is produced by rat mast cells in response to interleukin-1ß (Hogaboam et al, 1993) within a time frame of 30 min and influences the release of other inflarnmatory mediators (Hogaboam et al, 1993). As mast cells are often juxtaposed to blood vessels and afferent nerve endings (Holzer, 1992) it could be hypothesized that interleukin-lß acts on these cells to stimulate the sequential formation of NO and prostaglandins which, in turn, contribute to the sensitization of afferent nerve endings. In addition, NO generated in the rat skin can by itself give rise to afferent nerve-mediated vasodilatation (Holzer and Jocic, 1994).…”

“…The cutaneous vasodilatation induced by topical administration of capsaicin is to a large extent mediated by activation of thin afferent neiVe fibres and release of vasoactive peptides from their peripheral endings (Holzer, 1992). We have previously shown that the inflammatory cytokine interleukin-lß enhances the hyperaemia evoked by injection of capsaicin into the rat plantar hindpaw skin in a prostaglandin-dependent manner (Herbert and Holzer, 1994).…”

Interleukin‐1β enhances capsaicin‐induced neurogenic vasodilatation in the rat skin

“…These effects are elicited by activation of nociceptive afferent nerve fibres and release of vasoactive peptides from their peripheral endings. Among them, calcitonin gene-related peptide (CGRP) and substance P are the best studied candidate mediators (Holzer, 1992). The process of neurogenic inflammation is pathophysiologically relevant because it is potentially involved in a variety of diseases including inflammation of the skin, eye and respiratory tract, arthritis, migraine, and inflammatory bowel disease (Holzer, 1988;Maggi & Meli, 1988;Barnes, 1991;Basbaum & Levine, 1991;Moskowitz & Buzzi, 1991;Sharkey, 1992).…”

“…In addition to altering vascular functions, peptides released from afferent nerve endings can influence the activity of immunocompetent cells including mast cells, granulocytes, macrophages and lymphocytes (Donnerer et al, 1990;McGillis et al, 1990;Holzer, 1992). Mediators released from these cells, such as histamine and prostaglandins, can sensitize afferent nerve endings and in this way lead to hyperalgesia and prolong the inflammatory process (Handwerker, 1991).…”