Effects of nociceptin and nocistatin on antidromic vasodilatation in hairless skin of the rat hindlimb in vivo.
1. We tested whether nociceptin (NCE), the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor, and nocistatin (NST), which reverses central NCE effects when applied intrathecally (i.t.), affect small-diameter afferent fibre-mediated vasodilatation in rat hairless skin. 2. Female Wistar rats were vagotomized. Ongoing sympathetic vasoconstrictor activity was abolished by bilateral section of the lumbar sympathetic trunk between ganglia L2 and L3. Sensory axons were selectively stimulated in the dorsal root L5 by 20 electrical impulses supramaximal for activating C-fibres at 1 Hz. Blood flow was measured on the plantar skin of the left hind paw in the L5 dermatome using laser Doppler flowmetry. 3. NCE injected intravenously (i.v.) as single boluses (1, 10 and 100 nmol kg(-1) 7 - 8 min before dorsal root stimulation (n=6) dose-dependently decreased blood pressure and local vascular resistance and suppressed antidromic vasodilatation maximally by 47% (P<0.01). When NCE was injected 2 min before stimulation (n=3), antidromic vasodilatation was reduced by 64% after NCE (1 nmol kg-1) and totally, or almost totally, abolished after the two higher doses. 4. NST (1 - 100 nmol kg(-1) i.v., n=6) was without significant effect on blood pressure and cutaneous vascular resistance. Applied 5 (n=6) or 2 min (n=3) before stimulation it also did not affect antidromic vasodilatation. NST (100 nmol kg(-1) i.v.) applied shortly before an equimolar dose of NCE did not antagonize NCE effects on vascular resistance, blood pressure and antidromic vasodilatation (n=4). 5. In conclusion, NCE inhibits antidromic vasodilatation, a component of neurogenic inflammation, in rat skin while NST is without effect. NST, at the small-diameter sensory ending, is not an effective antagonist of NCE.
Häbler
H
H
Physiologisches Institut, Christian-Albrechts-Universität, Olshausenstrasse 40, 24098 Kiel, Germany. jhaebler@physiologie.uni-kiel.de
Timmermann
L
L
Stegmann
J
J
Jänig
W
W
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply* / Q000187:drug effects; D007278:Injections, Spinal; D017078:Laser-Doppler Flowmetry; D009412:Nerve Fibers / Q000187:drug effects; D018847:Opioid Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation; D014628:Vagotomy; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D000097629:Nociceptin
D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin; C111148:nocistatin