NO EFFECT OF D-MYO-INOSITOL-1,2,6-TRIPHOSPHATE ON VASOCONSTRICTION EVOKED BY NEUROPEPTIDE Y AND NONADRENERGIC 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 reponses 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 inihibition 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.