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.
De Wildt
D J
DJ
van der Beek
E M
EM
De Jong
Y
Y
Nijkamp
F P
FP
Kreeftenberg
J G
JG
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects* / Q000294:innervation; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D037342:Pertussis Toxin; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella
D000319:Adrenergic beta-Antagonists; D001427:Bacterial Toxins; D010276:Parasympatholytics; D011453:Prostaglandins; D010566:Virulence Factors, Bordetella; D003907:Dexamethasone; D037342:Pertussis Toxin; D007213:Indomethacin