Local regulation of skin blood flow during cooling involving presynaptic P2 purinoceptors in rats

Abstract

1 This study investigated a local effect of cooling on the plantar skin blood flow (PSBF) of tetrodotoxin-treated rats by laser-Doppler flowmetry. 2 When the air temperature around the left foot was locally cooled from 25 to 101C, the PSBF of the left foot decreased. 3 The response was inhibited by the a-adrenoceptor antagonist phentolamine, the a 1 -adrenoceptor antagonist bunazosin, the a 2 -adrenoceptor antagonist RS79948, and bretylium and guanethidine that inhibit noradrenaline release from sympathetic nerves. Adrenalectomy of the rats did not affect the cooling-induced response. 4 The P2 purinoceptor antagonists suramin and PPADS also significantly suppressed the coolinginduced reduction of PSBF. However, the inhibitory effect of PPADS on the cooling-induced response was abolished after the treatment with phentolamine. Intra-arterial injections of ATPgS, a stable P2 purinoceptor agonist, at 251C caused a transient decrease in PSBF in a dose-dependent manner, which was significantly inhibited by phentolamine and guanethidine. 5 These results suggest a novel mechanism for local cooling-induced reduction of skin blood flow in vivo; moderate cooling of the skin induces the release of ATP, which stimulates presynaptic P2 purinoceptors on sympathetic nerve terminals and facilitates the release of noradrenaline, thereby causing contractions of skin blood vessels via the activation of a 1 -and a 2 -adrenoceptors.

Purinergic Signaling in Healthy and Diseased Skin

“…In a later paper, it was suggested that cooling-induced reduction in skin blood flow was because of the ATP released from sympathetic nerves stimulating presynaptic P2 receptors on sympathetic nerve terminals to facilitate release of noradrenaline, resulting in constriction (Koganezawa et al, 2006). When skin temperature was increased, A 1 receptors mediated vasodilation (Stojanov and Proctor, 1990).…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…According to Koganezawa et al (2006), it was suggested that the cooling-induced reduction in skin blood flow was due to the ATP released from sympathetic nerves stimulating presynaptic P2 receptors on sympathetic nerve terminals to facilitate release of NA, resulting in constriction. Arteriolar contractile responses to nanomolar concentrations of topically applied adenosine acting at A 1 receptors in the skin microcirculation of hamsters were enhanced when local skin temperature was increased; vasodilator responses evoked by micromolar concentrations of adenosine were temperature insensitive (Stojanov and Proctor, 1990).…”

Peripheral Nervous System

“…Raynaud's Disease A physiological role for facilitatory P2 receptors in sympathetic nerves has been described, mainly in cooling-induced vasoconstriction in the skin (Koganezawa et al 2006). Cooling was shown to cause release of ATP that activated excitatory presynaptic P2 receptors in sympathetic nerve terminals to enhance NA release leading to vasoconstriction.…”