Effects of the neuropeptide YY1 receptor antagonist SR 120107A on sympathetic vascular control in pigs in vivo .
The possible involvement of neuropeptide Y in sympathetic vasoconstriction in various vascular beds in anesthetized pigs in vivo was studied using the neuropeptide Y Y1 receptor antagonist SR 120107A. Single impulse sympathetic nerve stimulation evoked rapid vasoconstrictor responses in hind limb and nasal mucosa which were not affected by SR 120107A (1.5 mg kg-1). Vascular responses to high frequency stimulation was measured in kidney, spleen (three 1 s bursts at 20 Hz or 300 impulses at 10 Hz), hind limb and nasal mucosa (three 1 s bursts at 20 Hz). High frequency stimulation evoked rapid vasoconstriction in all vascular beds studied. This was followed by a long-lasting phase of reduced blood flow in hind limb and nasal mucosa. SR 120107A (1.5 mg kg-1) attenuated the vasoconstriction evoked by the 20 Hz stimulation in the kidney, whereas a higher dose (a total of 6.0 mg kg-1) was required to reduce the vascular response in kidney to the 10 Hz simulation. SR 120107A (1.5 mg kg-1) did not inhibit the vascular responses in spleen, hind limb or nasal mucosa to the 20 Hz stimulation or the vasoconstriction in the spleen to the 10 Hz stimulation (a total of 6 mg kg-1). Subsequent addition of the adrenoceptor antagonists phenoxybenzamine (5 mg kg-1) plus timolol (2 mg kg-1) strongly reduced the vascular responses to single impulse stimulation and high frequency stimulation (20 Hz series) in all vascular beds. We conclude that endogenous neuropeptide Y acting on the neuropeptide Y Y1 receptor, as revealed by SR 120107A, is likely to account for part of the sympathetic vasoconstriction upon high frequency stimulation in the kidney.
Malmström
R E
RE
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Lundberg
J M
JM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D005263:Femoral Artery / Q000294:innervation; D006614:Hindlimb / Q000294:innervation; D007668:Kidney / Q000098:blood supply; D008297:Male; D008438:Maxillary Artery / Q000294:innervation; D009281:Naphthalenes / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000294:innervation; D009478:Neuropeptide Y / Q000097:blood / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013154:Spleen / Q000098:blood supply; D013552:Swine; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D009281:Naphthalenes; D009478:Neuropeptide Y; D011759:Pyrrolidines; D017476:Receptors, Neuropeptide Y; C093150:SR 120819A; D010643:Phenoxybenzamine