Mechanisms of the cutaneous vasodilator response to local external pressure application in rats: involvement of CGRP, neurokinins, prostaglandins and NO.
1. Local pressure-induced vasodilation (PIV) is a neural vasodilator response to non-nociceptive externally applied pressure in the skin, previously described in humans. We first determined whether PIV exists in rats and depends on capsaicin-sensitive fibres as it does in humans. We then examined the mediators involved in the efferent pathway of PIV. 2. Cutaneous blood flow was measured by laser Doppler flowmetry during 11.1 Pa s(-1) increases in local applied pressure in anaesthetized rats. The involvement of capsaicin-sensitive fibres in PIV was tested in rats treated neonatally with capsaicin. To antagonize CGRP, neurokinin-1, -2, or -3 receptors, different groups of rats were treated with CGRP(8 - 37), SR140333, SR48968 or SR142801, respectively. Prostaglandins involvement was tested with indomethacin treatment. To inhibit nitric oxide synthase (NOS) activity or specific neuronal NOS, rats were treated with N(G)-nitro-L-arginine or 7-nitroindazole, respectively. 3. PIV was found in rats, as in humans. PIV was abolished by neonatal treatment with capsaicin and by administration of CGRP(8 - 37) but remained unchanged with SR140333, SR48968 and SR142801 treatments. Prostaglandin inhibition resulted in a significant decrease in PIV. Inhibition of NOS abolished PIV, whereas inhibition of neuronal NOS caused a diminution of PIV. 4. These data suggest that PIV depends on capsaicin-sensitive fibres in rats, as in humans. It appears that CGRP plays a major role in the PIV, whereas neurokinins have no role. Furthermore, PIV involves a contribution from prostaglandins and depends on endothelial NO, whereas neuronal NO has a smaller role.
Fromy
B
B
Laboratoire de Physiologie, Faculté de Médecine d'Angers, F-49045 Angers, cedex France.
Merzeau
S
S
Abraham
P
P
Saumet
J L
JL
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D009569:Nitric Oxide / Q000378:metabolism; D011312:Pressure; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000502:physiology; D018042:Receptors, Neurokinin-3 / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D011453:Prostaglandins; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin