Human alveolar macrophage mediated vasodilation and the role of arginine compounds.
To determine whether human alveolar macrophages (AM) generate a compound similar to the endothelium-derived relaxing factor, we studied the effect of AM on the isometric response of the pre-contracted rat aorta preparation in the presence and absence of L-arginine or N-substituted L-arginine compounds. Addition of AM to the pre-contracted aorta preparation was ineffective even in the presence of millimolar concentrations of L-arginine. But, AM in the presence of the substituted L-arginine, N alpha-benzoyl L-arginine ethyl ester, significantly increased vasodilation. The enhanced relaxation was associated with an increase in vascular cyclic guanosine 3,5'-monophosphate formation. Hemoglobin and N omega-nitro L-arginine methyl ester are inhibitors of the endothelium-dependent relaxation, and both attenuated the vasodilation elicited by AM. Human AM were found to metabolize N alpha-benzoyl L-arginine ethyl ester to a citrulline derivative. No such metabolism was observed with L-arginine. A specific, high-pressure liquid chromatographic assay for guanidines revealed that the lack of effect of external L-arginine is not due to the presence of an excess amount of endogenous L-arginine in AM. These results demonstrate that nonactivated human AM, unlike rodent macrophages, possess an enzyme system(s) that metabolize(s) arginine derivatives but not L-arginine to a vasodilator, and this vasodilator has properties similar to that of endothelium-derived relaxing factor. This human AM-derived vasodilator may have an important role in regulating airway smooth muscle function.
Thomas
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G
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007.
Swartz
R P
RP
Yeager
H
H
Ramwell
P W
PW
D000328:Adult; D000818:Animals; D001011:Aorta; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006801:Humans; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation
D001120:Arginine; C009727:benzoylarginine ethyl ester; D006152:Cyclic GMP