Modulation of sympathetic vasoconstriction by sensory nerves and nitric oxide in rat irideal arterioles
Hill, C.E.; Gould, D.J.
Journal of Pharmacology and Experimental Therapeutics 273(2): 918-926
1995
ISSN/ISBN: 0022-3565 PMID: 7538584 Document Number: 452101
Transmural nerve stimulation of arterioles in the rat iris produces a vasoconstriction mediated via alpha-1B adrenoceptors and the mobilization of intracellular calcium. This study has investigated the role of sensory nerves in modulating this vasoconstriction using isolated preparations of iris perfused with Krebs' solution. Repeated stimulation of the transmural nerves for 1 sec (10 Hz), at intervals less than 2 min, produced a rapid and long-lasting loss of the vasoconstriction. This inhibition was not seen in arterioles taken from rats treated neonatally with capsaicin (50 mg/kg) nor after application of capsaicin (10-5 M) to control preparations. In arterioles from control rats, both the substance P analog Sar-9 and calcitonin gene-related peptide (CGRP) were effective in inhibiting nerve-mediated vasoconstriction. L-N-G-nitroarginine methyl ester (10-15 M) but not D-N-G-nitroarginine methyl ester (10-5 M), prevented the loss of vasoconstriction during repetitive stimulation, which suggested the involvement of nitric oxide. Antagonists to the NK-1 and NK-2 neurokinin receptor subtypes, RP 67580 and L-659877, respectively, were without effect, whereas the antagonist to the CGRP, receptor, CGRP-8-37, prevented the loss of vasoconstriction during repetitive nerve stimulation. The effects of both Sar-9 and CGRP (10-8 M) in inhibiting the nerve-mediated vasoconstriction were prevented by preincubation in L-N-G-nitroarginine methyl ester (10-5 M), which suggested that the mechanism of action of both peptides involved the release of nitric oxide. Immunohistochemical studies showed that the substance P and CGRP fibers did not form the perivascular plexuses seen in other vascular beds but instead crossed the arterioles at intervals of 30 to 40 mu-m, perpendicular to the axis of the vessel. At these points, the fibers were in close association with some of the fibers of the perivascular adrenergic nerve network. We conclude that CGRP released from sensory nerves can inhibit sympathetic nerve-mediated vasoconstriction in arterioles in the iris of the rat through the release of nitric oxide.