NORADRENERGIC AND PEPTIDERGIC SYMPATHETIC REGULATION OF CUTANEOUS MICROCIRCULATION IN THE RAT

Cutaneous microcirculatory changes were measured by laser-Doppler flow metry in response to electrical stimulation of sympathetic efferent fi bres of the rat's saphenous nerve. After perineural capsaicin (2%) pre treatment, electrical stimulation of the peripheral stump of the cut s aphenous nerve evoked a reduction in blood flow (vasoconstriction) fol lowed by a minimal enhancement. This late vasodilatation was further r educed by resiniferatoxin (1 mu g/kg i.v.), and vasoconstriction was a bolished by guanethidine (8 mg/kg i.v.), indicating the involvement of sensory and sympathetic fibres in the respective responses. The vasoc onstrictor response was analysed after blockade of antidromic vasodila tation by combined capsaicin-resiniferatoxin pretreatment. alpha-Adren oceptor antagonists (1 mg/kg phentolamine, 0.5 mg/kg prazosin and 1 mg /kg GYKI-12743 i-dioxanyl)-methylamino(propyl)-3(2H)-piridazinone hydr ochloride) inhibited, but did not eliminate the blood flow reduction e voked by 3 Hz stimulation. At 10 Hz stimulation significant inhibition was obtained only with GYKI-12743. No inhibition was observed with pr opranolol (10 mu g/kg) on any occasion. A functional neuropeptide Y an tagonist, alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate, PP56; 50 mg/kg i.v.), markedly diminished the vasocontrictor response remain ing after treatments with the alpha-adrenoceptor blocking agents. Inhi bition was more pronounced at 10 Hz. Since 3 Hz corresponds to an aver age, and 10 Hz approaches the maximal firing rate of the sympathetic e fferents, these results emphasise the significant role of neuropeptide Y in regulation of the cutaneous microcirculation by sympathetic fibr es under physiological circumstances, particularly a during high activ ity. (C) 1997 Elsevier Science B.V.