Negative chronotropic and inotropic responses to nicotine in rat right and left atria.
1. Comparison between the chronotropic and inotropic effects induced by nicotine in the right and left atrial muscles of rat was investigated. 2. Nicotine (300 microM and 1 mM) significantly produced negative chronotropic and inotropic effects in the right atrium. The effects were concentration-dependent, and reached a maximum about 30 sec after nicotine administration (1 mM). The responses were attenuated with time even during exposure to nicotine (desensitization). 3. In the left atrium, nicotine (300 microM and 1 mM) caused a negative inotropic effect. The depression was decreased with an increase in the frequencies of stimulation (1-3 Hz). The negative inotropic effect reached a maximum at approx. 60 sec later. 4. Nicotine (1 mM) caused a greater negative inotropic response in the right atrium than in the left atrium by 23% (stimulated at 3 Hz). The effects were not modified by atropine (1 microM) and hexamethonium (1 mM). 5. There was no difference between single and cumulative administrations of nicotine in both right and left atrial muscles. 6. These results suggest that the negative chronotropic and inotropic effects of nicotine may be due mainly to a direct action on the cell membrane of rat atria, accompanied with down regulation of nicotinic ACh receptors. The difference between the right and left atria could result from a different innervation of the autonomic nervous system.
Department of Pharmacology, Nara Medical University, Japan.
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Nakatani
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Nakashima
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Satoh
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D009538:Nicotine; D001285:Atropine