Influence of analgesic antipyretics on the central cardiovascular effects of clonidine in rats.
The centrally acting antihypertensive drug clonidine has been found to stimulate the synthesis of PGF2 alpha in the brain. Centrally administered PGF2 alpha, in turn, induces rises of blood pressure and heart rate. We therefore studied the influence of inhibitors of prostaglandin (PG) synthesis on the cardiovascular effects of clonidine in urethane-anaesthetised rats. Pretreatment with indomethacin or paracetamol (100 micrograms/rat into the fourth cerebral ventricle) antagonised the central hypotensive effect of clonidine (0.125-16.0 micrograms/rat into the fourth cerebral ventricle). The bradycardic effect of centrally administered clonidine was, however, enhanced by pretreatment with paracetamol but not influenced by indomethacin pretreatment. Sodium meclofenamate (100 micrograms/rat into the fourth cerebral ventricle) did not significantly affect the clonidine-induced changes in blood pressure and heart rate. These results suggest that the clonidine-induced hypotension on one hand and bradycardia on the other hand may be mediated by partly different mechanisms. An interference of the formation of PGF2 alpha with the cardiovascular effects of clonidine cannot be completely excluded since paracetamol pretreatment potentiated the bradycardic effect of clonidine. However, inhibitors of PG synthesis did not enhance but antagonised the hypotensive effect of clonidine. Therefore it is likely that the synthesis of PGF2 alpha does not interfere with the hypotensive effect of clonidine. Moreover, the antagonism of the hypotensive effect by inhibitors of PG synthesis suggests that some hypotensive metabolite of arachidonic acid in the brain could be involved in the central hypotensive effect of clonidine.
D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008469:Meclofenamic Acid / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats
D011460:Prostaglandins F; D000082:Acetaminophen; D008469:Meclofenamic Acid; D003000:Clonidine; D007213:Indomethacin