TACHYPHYLAXIS AND SENSITIZATION TO NICOTINE-INDUCED TACHYCARDIAC AND PRESSOR EFFECTS AFTER NICOTINE INFUSIONS

This work examined the effects of nicotine on mean arterial pressure a nd heart rate in non-anesthetized spinal rats. Nicotine (200 mg/kg) wa s administered as a single bolus, as infusions lasting 7.5, 15 or 30 m in, and as a post-infusion bolus. A nicotine bolus increased pressure and rate, These effects were less marked as the rate of infusion decre ased. The infusions affected differentially the effects of a subsequen t bolus. Thus, while tachycardia was decreased, the blood pressure ris e was increased. An initial transient bradycardia was observed after b olus administration, but not during infusions; this effect was unchang ed after post-infusion boluses, Pharmacological analysis indicated tha t tachycardia and bradycardia were predominantly due to ganglionic sti mulation, while adrenal;and sympathetic nerve catecholamine release pl ayed a major role in the presser response. These results indicate that stow nicotine infusions do not induce tachyphylaxis for all of the ca rdiovascular effects of a subsequent bolus, and that development of ac ute tolerance appears to depend on the mechanism of action of the resp onse.