L-thyroxine affects involvement of H1, 5-HT2, prostaglandin receptors and the endothelial NO system in allergic vascular response in guinea pigs

Dysfunction of the vascular system is involved in anaphylactic shock from antigen challenge. Chronic L-thyroxine (Thy) administration induces cardiac remodeling and multiple ion channelopathies which contribute to exacerbated cardiac arrhythmias and a change in vascular responses. We measured the changes in the allergic vascular response in a Thy model. The allergic vascular response developed rapidly by exposure to antigen with two components, a peak observed at 4 min and a declining second phase. In the Thy group, the peak was reduced and the tone in the second phase increased. The H-1 receptor blocker diphenhydramine (DPH) reduced the peak tension in both control and Thy groups, but increased the second phase in control and decreased the second phase in the Thy group. No effect of the H-2 blocker (famotidine) was observed. The 5-HT2 receptor antagonist ritanserin (RTS), the COX inhibitor indomethacin (IDM), and the lipoxygenase inhibitor caffeic acid (CFA) were more effective inhibitors in the Thy groups relative to the control group. Nitro-L-arginine (NLA), which is an NO synthase (NOS) inhibitor, enhanced peak tension in control, but not in the Thy group. The peak tension in the control group was also increased following hemoglobin (HB), which inactivates the NO pathway, by methylene blue (MTB), which suppresses cGMP formation, and by saponins, which destroy the endothelium. However, the same procedures were without effect in the Thy group. L-Arginine, an NO donor, produced a larger reduction of peak of tension in the Thy group relative to the control group. In conclusion, suppression of allergic vascular responses by DPH, RTS, CFA, and IDM was enhanced in the Thy model and the enhancement of these responses by NLA, HB, and MTB was abolished in this group. (C) 2003 Wiley-Liss, Inc.