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Nonadrenergic noncholinergic vasodilation in bovine ciliary artery involves CGRP and neurogenic nitric oxide
A K Wiencke1, H Nilsson, P J Nielsen
1Department of Pharmacology, University of Aarhus, Denmark.
Purpose:
Characterization of the nonadrenergic noncholinergic (NANC) vasodilator innervation in the anterior segment in the bovine eye.
Methods:
The neurogenic tetrodotoxin-sensitive response to electrical field stimulation (EFS) of the intraocular segment of the bovine long posterior ciliary artery supplying the ciliary body was recorded using isolated ring segments of this artery mounted on an isometric myograph. After adrenergic and cholinergic receptor blockade (with phentolamine, propranolol, and atropine), the preconstricted vessels were subjected to EFS by passing constant current pulses (0.3 msec, 35 mA, 0.5 to 32 Hz) between two electrodes on either side of the vessel segments.
Results:
EFS resulted in 60% relaxation of the active tone in 40 vessels. Treatment with capsaicin reduced the NANC response by 16 +/- 2% (P < 0.001) and inhibition of the NO synthase with 1 x 10(-4) M L-NOARG reduced the NANC response by 83 +/- 10% (P < 0.001). Desensitization of the vessels to substance P had no effect. The CGRP(8-37) fragment (1 x 10(-6) M) in the presence of 1 x 10(-4) M L-NOARG reversibly and competitively inhibited the NANC response. L-arginine partly antagonized the inhibition induced by L-NOARG. About 60% of the L-NOARG-sensitive component of the NANC response was inhibited by methylene blue. Combined incubation with capsaicin and L-NOARG nearly abolished the NANC response. The L-NOARG-sensitive/capsaicin-resistant relaxation was present in endothelium denuded vessels. The responses to EFS were blocked by TTX.
Conclusions:
The neurogenic NANC vasodilator response in the intraocular part of the bovine long posterior ciliary artery supplying the ciliary body is endothelium independent and consists of two components: a capsaicin-sensitive component mediated by CGRP released from sensory nerve endings and a larger L-NOARG sensitive component mediated by a direct "nitroxidergic" neurotransmission. The size of the nitroxidergic NANC response indicates that it has a physiological relevance in vivo.