Anaphylaxis of small arteries: putative role of nitric oxide and prostanoids

This study investigated possible implication of nitric oxide and prostanoids in anaphylactic reaction in small mesenteric and coronary arteries. Material and methods. Isolated arteries from guinea pigs, sensitized with 0.5 mL of horse serum or sham-sensitized, were challenged with 1% of horse serum in vitro. Contractile responses of arteries (normalized diameter, 350–450 μm) were recorded by a small blood vessel wire myograph. For inhibition of the release of NO or prostanoids, vessels were pretreated with N(G)-nitro-L-arginine methyl ester (30 μM) or indomethacin (10 μM), respectively. Results. Antigen challenge was followed by contraction of both coronary and mesenteric vessels. Two patterns of contraction were observed: 1) peak contraction – an immediate transient contraction of relatively high amplitude; this was the most common pattern; 2) biphasic: the initial peak contraction was followed by a slow growing contraction with low amplitude. Biphasic pattern was observed in 60% of the mesenteric vessels and 40% of the coronary vessels. Inhibition of NO synthase significantly increased the peak contraction in the coronary vessels and the second-phase contraction in the mesenteric vessels. Inhibition of cyclooxygenase caused a decrease in the peak and second-phase contraction of both the coronary and mesenteric vessels. Conclusions. Despite anaphylactic contraction, nitric oxide seems to be released from the endothelium following antigen challenge in the small coronary and mesenteric arteries. This may contribute to the development of hypotension during anaphylaxis. Prostanoids are playing a different role – the contracting products of cyclooxygenase pathway are important for the development of anaphylactic contraction of the small isolated arteries.

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.