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.
Sun
X
X
Department of Pharmacology, University of Göteborg, Sweden.
Edvinsson
L
L
Hedner
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology; D003655:Decerebrate State; D004155:Diphenhydramine / Q000494:pharmacology; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D006633:Histamine Antagonists / Q000494:pharmacology*; D007275:Injections, Intravenous; D007295:Inositol Phosphates / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009478:Neuropeptide Y / Q000633:toxicity*; D010656:Phenylephrine / Q000633:toxicity; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000633:toxicity
D000959:Antihypertensive Agents; D006633:Histamine Antagonists; D007295:Inositol Phosphates; D009478:Neuropeptide Y; D014667:Vasopressins; D010656:Phenylephrine; D002927:Cimetidine; D004155:Diphenhydramine; D011738:Pyrilamine; C059368:atrinositol