Modulation of sympathetic vasoconstriction by sensory nerves and nitric oxide in rat irideal arterioles.
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 Sar9 and calcitonin gene-related peptide (CGRP) were effective in inhibiting nerve-mediated vasoconstriction. L-NG-nitroarginine methyl ester (10(-5) M), but not D-NG-nitroarginine methyl ester (10(-5) M), prevented the loss of vasoconstriction during repetitive stimulation, which suggested the involvement of nitric oxide. Antagonists to the NK1 and NK2 neurokinin receptor subtypes, RP 67580 and L-659877, respectively, were without effect, whereas the antagonist to the CGRP1 receptor, CGRP8-37, prevented the loss of vasoconstriction during repetitive nerve stimulation. The effects of both Sar9 and CGRP (10(-8) M) in inhibiting the nerve-mediated vasoconstriction were prevented by preincubation in L-NG-nitroarginine methyl ester (10(-5) M), which suggested that the mechanism of action of both peptides involved the release of nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)
Hill
C E
CE
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra.
Gould
D J
DJ
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007498:Iris / Q000098:blood supply*; D009475:Neurons, Afferent / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*
D015220:Calcium Channels; D018013:Receptors, Neuropeptide; D009569:Nitric Oxide; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin