Endogenous vasodilators modulate pulmonary vascular anaphylaxis.
We examined the role of endothelium-derived nitric oxide during antigen-induced contraction in pulmonary arteries isolated from actively sensitized guinea pigs. Ovalbumin (10(-2) mg/ml)-induced contraction was not sustained, and tension returned to baseline within 15 min. Pretreatment with methylene blue (10(-5) M) increased both the amplitude and the duration of the contractile response in these tissues. At 15 min, tension remained elevated and was > 70% of the peak amplitude. Removal of the endothelium with saponin (200 micrograms/ml) increased the magnitude of the contraction by > 125%; however, the duration of the response was unaffected. After pretreatment with saponin, methylene blue no longer increased the amplitude of antigen-induced contraction but its effect on the duration was unchanged. Pretreatment with nitro-L-arginine methyl ester significantly increased the magnitude of the contraction in each of the tissues. These results suggest that the response of guinea pig pulmonary arteries to antigen is modulated by two types of endogenous vasodilators, endothelium-derived nitric oxide that inhibits the initial phase of the response and an endothelium-independent relaxing factor that is guanosine 3',5'-cyclic monophosphate dependent and attenuates the duration of anaphylactic contraction.
Kelly
L J
LJ
Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.
Undem
B J
BJ
Adams
G K
GK
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D006168:Guinea Pigs; D006454:Hemoglobins / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010047:Ovalbumin / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D012503:Saponins / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D006454:Hemoglobins; D012503:Saponins; D009569:Nitric Oxide; D010047:Ovalbumin; D001120:Arginine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester