Sensory nerves, nitric oxide and NANC vasodilatation.
Primary afferent neurons, originating from the dorsal root ganglia, provide a perivascular network of fibres around the arterial system throughout the body. When stimulated, these fibres cause a nonadrenergic noncholinergic (NANC) vasodilatation by release of calcitonin gene-related peptide (CGRP). This peptide is a potent vasodilator and, in this action, cooperates with nitric oxide (NO) in a tissue-specific manner. The hyperaemic effect of intravascularly injected rat CGRP-alpha in the rat gastric mucosa is reduced by blockade of the NO synthesis, which indicates that CGRP dilates the gastric microvascular bed via NO-dependent and -independent mechanisms. This is also true for endogenous CGRP, as the gastric mucosal hyperaemia, which is caused by gastric acid challenge and involves CGRP, is likewise blocked by inhibition of the NO synthesis. The CGRP/NO-mediated vasodilatation is an important element of a neural emergency system that strengthens the resistance of the gastric mucosa in the face of pending acid injury. In the rat skin, CGRP participates in neurogenic inflammatory processes but the cutaneous vasodilator action of exogenous CGRP and the CGRP-mediated vasodilatation, evoked by antidromic stimulation of afferent nerve fibres, do not depend on the formation of NO. This L-arginine-derived autacoid, however, plays a role in the release of CGRP from afferent nerve fibres in the skin since it contributes to the CGRP-mediated vasodilator responses to chemical irritation or immunological challenge via interleukin-1 beta. These data indicate that the type of interaction between CGRP and NO in causing a NANC vasodilatation varies with the vascular bed under study. Depending on the tissue, NO may facilitate the release of CGRP from afferent nerve fibres or be a secondary vasorelaxant messenger of the peptide.
Holzer
P
P
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Wachter
C
C
Heinemann
A
A
Jocic
M
M
Lippe
I T
IT
Herbert
M K
MK
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000294:innervation; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000502:physiology*; D005753:Gastric Mucosa / Q000098:blood supply*; D008833:Microcirculation / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014664:Vasodilation / Q000502:physiology*
D009569:Nitric Oxide; D000431:Ethanol; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester