Rat peritoneal neutrophils selectively relax vascular smooth muscle.
A vascular relaxing factor from oyster glycogen-elicited rat peritoneal neutrophils has been shown previously to possess a pharmacologic profile similar to that described for endothelium-derived-relaxing factor. The present experiments were designed to determine the in vitro tissue and species selectivity effects of the neutrophil-derived nitric oxide. Neutrophils (1 x 10(5) to 1 x 10(8) cells/10-ml organ chamber) were added to organ chambers filled with a physiological salt solution (37 degrees C; pH 7.4; 21% O2; 100 U/ml of superoxide dismutase) containing a ring or strip of an isolated tissue contracted with an appropriate contractile agent. Neutrophils caused relaxations in all vascular tissues tested, with the dog coronary artery being the most sensitive (IC50 approximately 1 x 10(5) cells), followed by the dog femoral artery, rabbit aorta and dog saphenous vein, respectively. In the rabbit fundic strip, approximately 1 x 10(7) cells were required to induce 50% relaxation, with 1 x 10(8) cells producing less than 35% relaxation in the dog, guinea pig and rat tracheas. In contrast, nitroprusside- and cromakalim-induced relaxations in all the smooth muscle tissues tested. The response to cromakalim was similar in all tissues with nitroprusside being more active in the vascular tissues. Methylene blue (1 x 10(-5) M) abolished the neutrophil induced relaxations in the rabbit aorta and dog femoral artery but had no effect on the responses to nitroprusside or cromakalim in the rabbit aorta, dog femoral artery or guinea pig trachea. Neutrophils, nitroprusside and cromakalim had limited effects on the spontaneously beating guinea pig right atria.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Experimental Therapeutics, Wyeth-Ayerst Research, Princeton, New Jersey.
T J
TJ
Rimele
S J
SJ
Armstrong
D
D
Grimes
R J
RJ
Sturm
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D016275:Atrial Function; D001578:Benzopyrans / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D019806:Cromakalim; D004285:Dogs; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D006162:Guanylate Cyclase / Q000378:metabolism; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D001578:Benzopyrans; D011758:Pyrroles; D019806:Cromakalim; D009599:Nitroprusside; D009569:Nitric Oxide; D006162:Guanylate Cyclase