HYPOTENSIVE EFFECTS OF [D-TYR(27,36),D-THR(32)]NEUROPEPTIDE Y(27-36)

An analogue of the 10 C-terminal amino acids of neuropeptide Y (NPY) c ontaining three D-isomeric substitutions (27-36-D) has been synthesize d and its cardiovascular activity studied in Sprague-Dawley (SD) and s pontaneously hypertensive (SHR) rats. intravenous administration of 10 00 nmol/kg 27-36-D decreases MAP in SHR (-59.9 +/- 5.0 mmHg) and SD ra ts (-44.4 +/- 4.7,nmHg). The hypotension produced by 1000 nmol/kg 27-3 6-D diminished by 71.2% following pretreatment with the histamine rece ptor antagonist diphenhydramine, although histamine depletion with com pound 48/80 does not significantly alter this hypotension. These data suggest that NPY(27-36)-D produces a profound and sustained hypotensio n in two strains of rat which is partially attributable to activity at histamine receptors.