Recombinant human granulocyte colony-stimulating factor reverts vascular dysfunction.
The aim of our study was to investigate the vascular effects of recombinant human granulocyte colony-stimulating factor (rh G-CSF) in a rat model of irreversible vascular failure. Male anesthetized rats were subjected to the clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock) characterized by high mortality rate (0% survival, 120 min following the release of clamps), a profound hypotension and vascular dysfunction consisting of a marked hyporeactivity to phenylephrine (PE 1 nM-10 microM) of aortic rings. Administration of recombinant human granulocyte colony-stimulating factor (20 micrograms/kg i.v. 5 min after the release of occlusion) increased survival rate (90% 4 h after the release of occlusion), blunted the profound hypotension and reverted the marked vascular dysfunction. Finally, rh G-CSF inhibited the activity of inducible nitric oxide synthase in peritoneal macrophages activated with endotoxin. Our data suggest that rh G-CSF may influence vascular function when low-flow states occur.
Squadrito
F
F
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Altavilla
D
D
Squadrito
G
G
Campo
G M
GM
Ioculano
M
M
Serranò
M
M
Minutoli
L
L
Arlotta
M
M
Musolino
C
C
Saitta
A
A
Caputi
A P
AP
D000208:Acute Disease; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014652:Vascular Diseases / Q000188:drug therapy* / Q000473:pathology
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019001:Nitric Oxide Synthase