Neutrophil-derived relaxing factor relaxes vascular smooth muscle through a cGMP-mediated mechanism.
Neutrophils harvested from the peritoneal cavities of rats have been shown to release a factor that relaxes precontracted aorta and has a pharmacologic profile similar to that previously reported for endothelium-derived relaxing factor (EDRF). The present study was designed to determine if this neutrophil-derived relaxing factor (NDRF) relaxes rat aortic smooth muscle by affecting the intracellular cGMP levels. Aortic sheets (endothelium removed) were incubated in organ chambers in a physiological salt solution containing phenylephrine (1 x 10(-7) M) and superoxide dismutase (10 or 100 U/ml). Basal cGMP levels (10-15 pmoles/g tissue) were not affected by the incubation reagents. Neutrophils (3 x 10(6) to 1 x 10(8) cells/10 ml) increased cGMP, but not cAMP, levels in a cell number-dependent manner. Peak induction occurred at 5 min of incubation. Methylene blue (1 x 10(-5) M) inhibited and zaprinast (1 x 10(-5) M) potentiated the neutrophil-induced increases in cGMP. The data thus support the hypothesis that neutrophil-induced vascular smooth muscle relaxation is mediated through a factor, NDRF, which increases intracellular cGMP levels.
Lee
D K
DK
Department of Experimental Therapeutics, Wyeth-Ayerst Research, Princeton, NJ 08543.
Faunce
D
D
Henry
D
D
Sturm
R J
RJ
Rimele
T
T
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology; D010656:Phenylephrine / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013482:Superoxide Dismutase / Q000494:pharmacology
D011688:Purinones; D010656:Phenylephrine; D009569:Nitric Oxide; D000242:Cyclic AMP; D013482:Superoxide Dismutase; C011145:zaprinast; D006152:Cyclic GMP; D008751:Methylene Blue