Vinblastine attenuates endotoxin-induced impairment of CGMP-mediated pulmonary vasorelaxation.
We tested the hypothesis that neutrophils contribute to endotoxin-induced impairment of endothelium-dependent and -independent cyclic guanosine monophosphate (cGMP)-mediated pulmonary vascular smooth muscle relaxation. Rats were studied 6 h after endotoxin (20 mg/kg, intraperitoneal) or saline (1 cc, intraperitoneal). Neutrophil-depleted rats were studied 4 days after administration of vinblastine (750 micrograms/kg, intravenous). Concentration-response curves were generated for acetylcholine and sodium nitroprusside in isolated pulmonary arterial rings (10(-9) M to 10(-6) M). The absolute neutrophil count of controls was 1050 +/- 206 neutrophils/mL, and the absolute neutrophil count of vinblastine-treated rats was 100 +/- 41 neutrophils/mL (p < .05 versus controls) and 25 +/- 25 neutrophils/mL in vinblastine-treated rats receiving endotoxin (p < .05 versus control and endotoxin). Endotoxin-induced impairment of endothelium-dependent and -independent cGMP-mediated pulmonary vasorelaxation was significantly attenuated by prior treatment with vinblastine. We conclude that neutrophils contribute to the pathogenesis of endotoxin-induced impairment of cGMP-mediated pulmonary vascular smooth muscle relaxation.
Sheridan
B C
BC
Department of Surgery, University of Colorado, Denver, USA.
McIntyre
R C
RC
Meldrum
D R
DR
Cleveland
J C
JC
Agrafojo
J
J
Eisenach
J H
JH
Fullerton
D A
DA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009195:Peroxidase / Q000032:analysis; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014747:Vinblastine / Q000494:pharmacology*
D004731:Endotoxins; D009599:Nitroprusside; D014747:Vinblastine; D009195:Peroxidase; D006152:Cyclic GMP; D000109:Acetylcholine