Prejunctional regulation of reserpine-resistant sympathetic vasoconstriction and release of neuropeptide Y in the pig.
The prejunctional regulation of non-adrenergic sympathetic vasoconstriction and release of neuropeptide Y (NPY) was investigated in vivo. In reserpinized pigs (with depleted noradrenaline (NA)), it was demonstrated that brief sympathetic nerve stimulation (2 pulses of 20 Hz) of the spleen, kidney and hind limb in the presence of the alpha 2-adrenoceptor agonist UK 14,304 (1 micrograms/kg per min i.v.) evoked reproducible vasoconstrictor responses which were reduced by 40-80% in comparison to that in the absence of UK 14,304. In addition, the splenic overflow of NPY-like immunoreactivity (-LI) was reduced. After cessation of the UK 14,304 infusion all these effects were reversed by addition of the alpha 2-adrenoceptor antagonist yohimbine (0.2 mg/kg i.v.). Also the Y2 receptor agonist NPY(13-36) reduced the splenic overflow of NPY-LI. Splenic vasoconstriction per se was evoked by another Y2 receptor agonist N-acetyl[Leu28Leu31]NPY(24-36), while no vascular effects in the kidney or hind limb were observed. Both Y2 agonists displaced [125I]NPY binding to splenic membranes with higher potency than the Y1-receptor agonist [Leu31Pro34]NPY(1-36). No evidence was obtained for angiotensin II mechanisms being important for the enhanced NPY release after reserpine in spite of elevated renin release. The present results show that in the absence of NA, repetition of brief sympathetic nerve stimulation evokes vascular effects and NPY-LI release which are repeatable and these effects are efficiently modulated via alpha 2-adrenoceptors. Furthermore, the Y2 receptors may mediate both prejunctional inhibition of NPY release, as well as postjunctional vasoconstrictor effects in the pig spleen.
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Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Pernow
J
J
Lundberg
J M
JM
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D007668:Kidney / Q000502:physiology; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology*; D013552:Swine; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
D009478:Neuropeptide Y; D010656:Phenylephrine; D012110:Reserpine