EFFECT OF NEUROPEPTIDE-Y ON ENDOTOXIN-INDUCED SUPPRESSION OF THE RESPONSE TO VARIOUS AGONISTS IN CONSCIOUS RATS

Hypotension during endotoxic shock is related to reduced vascular responsiveness to vasoconstrictors. Neuropeptide Y (NPY) is known to potentiate the presser response to some agonists, and NPY infusion has been shown to improve hemodynamics and survival in endotoxemic rats. We therefore studied the effect of NPY infusion on the suppressed presser effect of norepinephrine (NE), angiotensin II (AII), vasopressin (VP), and endothelin (ET) in-conscious endotoxemic rats. Chronically cannulated conscious rats were infused with a non-hypotensive dose of endotoxin (LPS, 10 mu g/10 mu l/min) throughout the experiment. Infusion of NPY, 40 pmol/10 mu l/min was started 15 minutes before the LPS infusion, and continued for 65 minutes. Five minutes after the termination of NPY infusion, increasing agonist doses were administered i.v. to construct dose-response curves. Each experiment included one control group where saline replaced LPS, and one control group where saline replaced NPY. LPS infusion caused suppression of the presser responses to all four agonists, as expressed by ED(50) and by decreased presser response to the individual agonist doses. In addition, LPS infusion altered the bradycardic response to AII and ET. NPY infusion prior to the administration of NE, AII and VP resulted in partial reversal of the LPS-induced suppressed responsiveness to these agonists. NPY infusion had no effect on the response to ET in either control or endotoxemic rats. Partial reversal of the suppressed responsiveness to the three agonists by NPY infusion may contribute to the observed NPY-induced improvement of brood pressure and survival rate during endotoxic shock.