Tachyphylaxis and sensitization to nicotine-induced tachycardiac and pressor effects after nicotine infusions.
This work examined the effects of nicotine on mean arterial pressure and heart rate in non-anesthetized spinal rats. Nicotine (200 mg/kg) was administered as a single bolus, as infusions lasting 7.5, 15 or 30 min, and as a post-infusion bolus. A nicotine bolus increased pressure and rate. These effects were less marked as the rate of infusion decreased. The infusions affected differentially the effects of a subsequent bolus. Thus, while tachycardia was decreased, the blood pressure rise was increased. An initial transient bradycardia was observed after bolus administration, but not during infusions; this effect was unchanged after post-infusion boluses. Pharmacological analysis indicated that tachycardia and bradycardia were predominantly due to ganglionic stimulation, while adrenal and sympathetic nerve catecholamine release played a major role in the pressor response. These results indicate that slow nicotine infusions do not induce tachyphylaxis for all of the cardiovascular effects of a subsequent bolus, and that development of acute tolerance appears to depend on the mechanism of action of the response.
Cruz
S L
SL
Sección de Terapéutica Experimental, Departamento de Farmacología y Toxicología, CINVESTAV, IPN, México, D.F.
Vidrio
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology; D003655:Decerebrate State; D004334:Drug Administration Schedule; D005730:Ganglionic Blockers / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D006145:Guanethidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013565:Sympatholytics / Q000494:pharmacology; D013610:Tachycardia / Q000139:chemically induced / Q000503:physiopathology; D013618:Tachyphylaxis; D014628:Vagotomy
D005730:Ganglionic Blockers; D005731:Ganglionic Stimulants; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D013565:Sympatholytics; D018738:Hexamethonium; D009538:Nicotine; D006145:Guanethidine