Sympathetic vascular control of the pig nasal mucosa (2): Reserpine-resistant, non-adrenergic nervous responses in relation to neuropeptide Y and ATP.
The possible occurrence of non-adrenergic mechanisms in the sympathetic vascular control of the nasal mucosa was studied in vivo using reserpine-treated pigs (1 mg kg-1, i.v., 24 h earlier) in combination with pharmacological blockade of alpha-adrenoceptors by local phenoxybenzamine (1 mg kg-1, i.a.) infusion. The nasal mucosal depletion (99%) of the content of noradrenaline (NA) in reserpinized animals was not influenced by preganglionic denervation while the depletion (44%) of neuropeptide Y (NPY) was prevented. Upon stimulation with single shocks, 25% of the arterial blood flow reduction and 47% of the nasal mucosal volume reduction (reflecting contraction of venous sinusoids) were still present after reserpine as compared with controls. In reserpinized animals, the vascular responses were slow developing and long-lasting, and about 60% remained at 0.59 Hz and more than 80% at 6.9 Hz. The vascular effects after reserpine were, however, subjected to fatigue, which may explain why phenoxybenzamine treatment still reduced the functional effects in the absence of NA. Local intra-arterial injections of NA, NPY and the metabolically stable adenosine-5'-triphosphate analogue alpha, beta-methylene ATP (mATP) caused reduction in both arterial blood flow and nasal mucosal volume. The C-terminal fragment of NPY (NPY 13-36) also induced nasal vasoconstriction although with a fivefold lower potency than NPY 1-36. Adenosine-5'-triphosphate caused a biphasic vascular effect with vasodilatatory actions at low doses and a short-lasting vasoconstriction followed by vasodilatation at very high doses (100-fold higher than the threshold response to mATP). In contrast to the response to NA, the long-lasting vascular effects of NPY and mATP were resistant to phenoxybenzamine treatment. In conclusion, although NA is likely to mediate most of the sympathetic vascular responses to low-frequency stimulation in the pig nasal mucosa, a large resistance and capacitance vessel component upon high-frequency stimulation seems to be non-adrenergic and mimicked by NPY rather than ATP.
Lacroix
J S
JS
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Stjärne
P
P
Anggård
A
A
Lundberg
J M
JM
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D004558:Electric Stimulation; D005728:Ganglia, Sympathetic / Q000187:drug effects*; D007269:Injections, Intra-Arterial; D009297:Nasal Mucosa / Q000098:blood supply*; D009478:Neuropeptide Y / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D009478:Neuropeptide Y; D012110:Reserpine; D000255:Adenosine Triphosphate