No effect of D-myo-inositol-1,2,6-triphosphate on vasoconstriction evoked by neuropeptide Y and non-adrenergic sympathetic nerve stimulation.
The effects of the proposed neuropeptide Y (NPY) antagonist, D-myo-inositol-1,2,6-triphosphate (PP56), on vasoconstrictor responses evoked by NPY and non-adrenergic sympathetic nerve stimulation were investigated in the pig in vivo. Under control conditions, exogenous NPY evoked a dose-dependent increase in arterial blood pressure and vasoconstriction in spleen, kidney and skeletal muscle. After administration of PP56 (50 mg/kg), which transiently reduced systemic blood pressure by 18 +/- 5 mm Hg, the vascular responses evoked by NPY did not differ from those observed under control conditions. Stimulation of the splenic nerve and the lumbar sympathetic chain with 20-Hz burst activity in reserpine-pretreated pigs, which are devoid of their noradrenaline content, decreased splenic and hindlimb vascular conductance by 67 +/- 7 and 57 +/- 7%, respectively, under control conditions. In the presence of PP56 the nerve stimulation-evoked reductions in splenic and hindlimb vascular conductance were slightly but not significantly reduced to 59 +/- 9 and 48 +/- 7%, respectively. It is concluded that PP56 in the presently used high dose, which causes non-selective inhibition of vasoconstriction in the rat, cannot be used as an antagonist of vasoconstrictor responses evoked by NPY or non-adrenergic sympathetic nerve stimulation in the pig.
Pernow
J
J
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Modin
A
A
Lundberg
J M
JM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D006614:Hindlimb / Q000098:blood supply; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000494:pharmacology*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D013154:Spleen / Q000098:blood supply; D013552:Swine; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D007295:Inositol Phosphates; D009478:Neuropeptide Y; D012110:Reserpine; C059368:atrinositol