Endogenous neuropeptide Y mediates vasoconstriction during endotoxic and hemorrhagic shock.
Neuropeptide Y (1-36), NPY, is a sympathetic vasoconstrictor whose activities in blood vessels is determined by the presence of vasoconstrictive Y1 receptors and the enzyme dipeptidyl peptidase IV (DPPIV), which converts NPY to non-vasoconstrictive peptides. While the role of the NPY system has been established during cold water stress, its role in hypotensive conditions has not; yet, exogenous NPY improves hemodynamics and survival in rats with endotoxic shock. We used a new selective non-peptidergic Y1 receptor antagonist, BIBP-3226, to determine the role of the endogenous NPY/Y1 system in endotoxic shock (induced by i.v. injection of 10 mg/kg of Escherichia coli lipopolysaccharide 0127:B8, LPS) and hemorrhagic shock (bleeding of 15 ml/kg over 1.5 min). Conscious rats received a bolus of BIBP-3226 or the vehicle 5 min before endotoxin challenge or induction of hemorrhage, followed by continuous infusion. Mean arterial pressure (MAP) at 5 min after LPS administration dropped in the control group by 15%, compared to 36% in the BIBP-3226-treated group (p < 0.01). Similarly, the hemorrhage-induced drop in MAP in the control group was 32% at 5 min, compared to 53% in the BIBP-treated rats (p < 0.01). Plasma NPY levels were unchanged in the endotoxic shock group, but were significantly elevated in the hemorrhagic shock group. BIBP-3226 pretreatment abrogated the increased plasma NPY levels after hemorrhagic shock. Endogenous NPY contributes to blood pressure recovery during endotoxic and hemorrhagic shock.
Qureshi
N U
NU
Georgetown University Children's Medical Center, and Department of Physiology and Biophysics, Georgetown University, Washington, DC 20007, USA.
Dayao
E K
EK
Shirali
S
S
Zukowska-Grojec
Z
Z
Hauser
G J
GJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009478:Neuropeptide Y / Q000097:blood / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000502:physiology; D012771:Shock, Hemorrhagic / Q000209:etiology / Q000503:physiopathology*; D012772:Shock, Septic / Q000209:etiology / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
C092926:BIBP 3226; D008070:Lipopolysaccharides; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine