Noradrenergic and peptidergic sympathetic regulation of cutaneous microcirculation in the rat.
Cutaneous microcirculatory changes were measured by laser-Doppler flowmetry in response to electrical stimulation of sympathetic efferent fibres of the rat's saphenous nerve. After perineural capsaicin (2%) pretreatment, electrical stimulation of the peripheral stump of the cut saphenous nerve evoked a reduction in blood flow (vasoconstriction) followed by a minimal enhancement. This late vasodilatation was further reduced by resiniferatoxin (1 microg/kg i.v.), and vasoconstriction was abolished by guanethidine (8 mg/kg i.v.), indicating the involvement of sensory and sympathetic fibres in the respective responses. The vasoconstrictor response was analysed after blockade of antidromic vasodilatation by combined capsaicin-resiniferatoxin pretreatment. alpha-Adrenoceptor antagonists (1 mg/kg phentolamine, 0.5 mg/kg prazosin and 1 mg/kg GYKI-12743 (RS-2-(3)N-(2-benzo;1,4i-dioxanyl)-methylamino(propyl)-3(2H) -piridazinone hydrochloride) inhibited, but did not eliminate the blood flow reduction evoked by 3 Hz stimulation. At 10 Hz stimulation significant inhibition was obtained only with GYKI-12743. No inhibition was observed with propranolol (10 microg/kg) on any occasion. A functional neuropeptide Y antagonist, alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate, PP56; 50 mg/kg i.v.), markedly diminished the vasocontrictor response remaining after treatments with the alpha-adrenoceptor blocking agents. Inhibition was more pronounced at 10 Hz. Since 3 Hz corresponds to an average, and 10 Hz approaches the maximal firing rate of the sympathetic efferents, these results emphasise the significant role of neuropeptide Y in regulation of the cutaneous microcirculation by sympathetic fibres under physiological circumstances, particularly during high activity.
Pintér
E
E
Department of Pharmacology, University Medical School of Pécs, Hungary. peri@apacs.pote.hu
Helyes
Z
Z
Pethö
G
G
Szolcsányi
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D007295:Inositol Phosphates / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009476:Neurons, Efferent / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007295:Inositol Phosphates; D009478:Neuropeptide Y; D010975:Platelet Aggregation Inhibitors; D011724:Pyridazines; C064892:GYKI 12743; C059368:atrinositol; D009638:Norepinephrine