Effects of dexamethasone and indomethacin on the vascular beta 2-adrenolytic action of pertussis toxin in rats; a prostaglandin-mediated phenomenon.

Lymphocytosis promoting factor (LPF), alternatively described as pertussis toxin, inhibits the vasodilation after beta 2-adrenoceptor stimulation with salbutamol as well as the negative chronotropic activity induced by the muscarinic receptor stimulant arecoline 4 days after vaccination of rats. To analyse whether arachidonic acid metabolites contributed to these phenomena the cyclo-oxygenase inhibitor indomethacin and the phospholipase A2 inhibitor dexamethasone were administered over a period of 4 days. Pretreatment with either drug restored beta 2-adrenoceptor responsiveness. The cardiac anticholinergic effect, however, was not changed. Interestingly, neither of the inhibitors prevented the blood pressure lowering effect of LPF. The reversing effect on vascular beta 2-hyporesponsiveness of indomethacin and dexamethasone therefore appears to be rather specific. It is concluded that endogenous prostaglandins may participate in the vascular beta 2-adrenergic impairment caused by LPF. Furthermore, the results are considered in view of desensitization theories and underlying mechanisms of LPF-induced autonomic impairment.