Antagonism by E. coli endotoxin of some cardiovascular effects induced in the rat by two alpha 2-adrenoceptor agonists.
E. coli endotoxin (0.01, 0.1 and 1 microgram/kg i.v.) 1 h before alpha 2-adrenoceptor agonists B-HT 933 and clonidine (i.v.) antagonized their bradycardiac and hypotensive effects in intact rats. This antagonism seems not to depend on the presence of the adrenal glands since similar results were obtained in adrenalectomized rats. Endotoxin at higher doses (1 and 10 micrograms/kg) suppressed the hypotensive and reduced the bradycardiac effect of clonidine injected i.c.v. (5 micrograms/kg). In contrast, endotoxin (up to 100 micrograms/kg) did neither increase arterial pressure nor heart rate in the pithed rat. This suggests the participation of a central site of action for endotoxin. However, E. coli endotoxin (1, 10 or 100 micrograms/kg) did not decrease the inhibition by clonidine of the tachycardia induced by stimulation of the cardioacceleratory nerve. This excludes peripheral presynaptic alpha 2-adrenoceptor blockade by endotoxin. Only 100 micrograms/kg decreased the pressor response to clonidine in the pithed rat. These results show that E. coli endotoxin is a potent modificator of the cardiovascular regulation in the rat. It antagonized central alpha 2-adrenoceptor mediated cardiovascular effects at doses lower than those acting on postsynaptic peripheral alpha-adrenoceptors.
D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors*; D000818:Animals; D001381:Azepines / Q000037:antagonists & inhibitors; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D003000:Clonidine / Q000037:antagonists & inhibitors; D004110:Diltiazem / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D004731:Endotoxins; C015603:azepexole; D004110:Diltiazem; D003000:Clonidine