Histamine-independent modulation of the neuropeptide Y-induced pressor response by alpha-trinositol in the pithed rat.

The modulatory effects of alpha-trinositol (D-myo-inositol-1.2.6- trisphosphate; PP 56) on the systemic arterial blood pressor responses induced by neuropeptide Y, preganglionic nerve stimulation, phenylephrine and vasopressin were studied in pithed rats. Intravenous administration (within 2 min.) of alpha-trinositol reduced the neuropeptide Y-induced increase in mean arterial pressure within a defined dose range without altering the heart rate. The influence of alpha-trinositol on the neuropeptide Y-induced pressor response in the presence of non-selective as well as H1- and H2-selective histamine antagonists (diphenhydramine, mepyramine and cimetidine respectively) were investigated. The maximal increase in mean arterial pressure induced by neuropeptide Y as well as the duration of the pressor response was enhanced after nonselective (diphenhydramine) or H1-selective (mepyramine) histamine blockade. The enhancement of the neuropeptide Y-induced pressor response by the H1 specific antagonist mepyramine was significantly more pronounced compared to the H2-selective agent. The exaggerated increase in mean arterial pressure in response to neuropeptide Y after histamine blockade was inhibited by alpha-trinositol to a similar extent as without such pretreatment. We conclude that neuropeptide Y interacts with histamine in the pithed rat and that this action may partially offset the pressor actions of the peptide. The neuropeptide Y-induced pressor responses may be inhibited by alpha-trinositol within a defined dose range indicating that this non-peptide agent may act as a functional inhibitor to neuropeptide Y in vascular tissue.