Calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) levels are elevated in plasma and decreased in vena cava during endotoxin shock in the rat.
Calcitonin gene-related peptide (CGRP), a potent vasodilator, and neuropeptide Y (NPY), a potent vasoconstrictor and potentiator of norepinephrine-induced vasoconstriction, were examined in an animal model of endotoxin shock. Gram-negative bacterial endotoxin (lipopolysaccharide B from Salmonella enteritidis) was administered as a bolus (16.7 mg/kg, i.v.) to conscious, unrestrained rats, previously cannulated for blood pressure measurements and blood withdrawal. At 30 min, endotoxin caused 35-40 mm Hg drop in mean arterial pressure and significant increases in heart rate and plasma levels of glucose and lactate. By 3 hr, blood pressure had returned to near normal levels and remained normal until cardiovascular collapse at 4-6 hr (approximately 70% of the rats). Endotoxin elevated plasma CGRP levels by fourfold at 30 min and 22-fold at 3 hr. Of the organs tested, only vena cava showed significant decreases in CGRP levels. Endotoxin also elevated plasma NPY levels by 67% and decreased NPY levels in adrenal gland and vena cava at 30 min and 3 hr. The data suggest that both CGRP and NPY are released into the circulation during development of endotoxin shock in the rat. NPY may contribute to the compensatory mechanism, tending to bring arterial pressure back to normal levels during intermediate stages of endotoxemia. CGRP, because of its extremely high potency as a hypotensive agent, may contribute to the hypotension at both early and late stages during pathogenesis of endotoxin shock.
Wang
X
X
Department of Physiology, Loyola University Medical Center, Maywood, Illinois.
Jones
S B
SB
Zhou
Z
Z
Han
C
C
Fiscus
R R
RR
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood*; D004731:Endotoxins / Q000633:toxicity; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000097:blood* / Q000378:metabolism; D014684:Venae Cavae / Q000737:chemistry*
D004731:Endotoxins; D009478:Neuropeptide Y; D015740:Calcitonin Gene-Related Peptide