Interaction between clonidine and physostigmine in normal rats and in rats after sinoaortic denervation.
Clonidine (3-30 micrograms.kg-1, i.v.) induced a fall in mean arterial pressure in rats after sinoaortic denervation but not in sham-operated animals. Moreover, sinoaortic denervation reduced the bradycardic action of this antihypertensive drug. Pressor and tachycardic response to physostigmine (60 micrograms.kg-1, i.v.) were greater in denervated than in sham-operated rats. The increase of mean arterial pressure was 26.2 +/- 2.2 mm Hg in sham-operated rats (n = 12) and 53.8 +/- 2.0 mm Hg in denervated rats (n = 12, P less than 0.005). Pretreatment with 3 micrograms.kg-1 (i.v.) of clonidine did not alter the pressor response to physostigmine (60 micrograms.kg-1) in either of the two groups; 10 and 30 micrograms.kg-1 of clonidine reduced the physostigmine-induced increase of mean arterial pressure in sham-operated rats but enhanced the pressor response in denervated animals. Furthermore, an ineffective dose of physostigmine (30 micrograms.kg-1, i.v.) induced a pressor response after pretreatment with clonidine (10 micrograms.kg-1) in denervated rats. Clonidine (10 micrograms.kg-1) did not affect the pressor effect of 1,1 dimethyl-4-phenylpiperazinium iodide (DMPP: 50 micrograms.kg-1, i.v.) or phenylephrine (4 micrograms.kg-1, i.v.) in either group. The anticholinergic effect of clonidine in sham-operated rats may be explained by an inhibitory action on the release of acetylcholine in several brain structures but the facilitatory effect of clonidine observed in denervated animals is not clear. The results did not suggest a peripheral involvement in this facilitatory effect.
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Cátedra de Farmacologia, Facultad de Farmacia y Bioquímica, UBA, Instituto de Investigaciones Farmacológicas, CONICET, Buenos Aires, Argentina.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D003714:Denervation; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D012849:Sinoatrial Node / Q000502:physiology*
D010656:Phenylephrine; D004246:Dimethylphenylpiperazinium Iodide; D010830:Physostigmine; D003000:Clonidine