Hypotensive effects of [D-Tyr27,36, D-Thr32]Neuropeptide Y (27-36).
An analogue of the 10 C-terminal amino acids of neuropeptide Y (NPY) containing three D-isomeric substitutions (27-36-D) has been synthesized and its cardiovascular activity studied in Sprague-Dawley (SD) and spontaneously hypertensive (SHR) rats. Intravenous administration of 1000 nmol/kg 27-36-D decreases MAP in SHR (-59.9 +/- 5.0 mmHg) and SD rats (-44.4 +/- 4.7 mmHg). The hypotension produced by 1000 nmol/kg 27-36-D diminished by 71.2% following pretreatment with the histamine receptor antagonist diphenhydramine, although histamine depletion with compound 48/80 does not significantly alter this hypotension. These data suggest that NPY (27-36)-D produces a profound and sustained hypotension in two strains of rat which is partially attributable to activity at histamine receptors.
Roscoe
A K
AK
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Leach
S M
SM
Nyce
J W
JW
Wooles
W R
WR
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004155:Diphenhydramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D011968:Receptors, Histamine / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D006634:Histamine H1 Antagonists; D009478:Neuropeptide Y; D010446:Peptide Fragments; D011968:Receptors, Histamine; C095005:neuropeptide Y (27-36), Tyr(27,36)-Thr(32)-; D004155:Diphenhydramine