Blood platelet function after chronic treatment of rats and guinea pigs with nicotine.
To establish whether long-term application of nicotine can at all alter thrombocyte function, the alkaloid was administered to rats and guinea pigs for up to 8 weeks, using subcutaneously implanted ALZET minipumps. These two species were examined, since rat platelets are known to possess both alpha 2- and beta 2-adrenoceptors, whereas guinea pig platelets have practically none of either type. Platelet activity was assessed ex vivo by determining rates of ADP-induced aggregation and by applying a new in vitro technique giving a measure of primary hemostasis. Nicotine in doses of 2 mg/kg/day (rats) and 10 mg/kg/day (guinea pigs), continuously applied over 8 weeks, yielded alkaloid plasma levels in the respective species in the same range as found for smokers. This chronic in vivo pretreatment had no discernible effect on platelet function. However, platelets from rats having received the higher dose of 10 mg nicotine/kg/day for 8 weeks required a significantly higher concentration of ADP to induce the half-maximal rate of aggregation. Concomitantly, the in vitro determined bleeding time doubled. The nicotine-induced decrease in platelet sensitivity towards ADP could be prevented by simultaneously treating the rats with the beta-blocker propranolol. Adrenaline applied chronically to rats for 8 weeks stimulated platelet response instead of mimicking nicotine effects. The unexpected inhibition of rat platelet function at higher alkaloid-dosage thus seems to be an indirect nicotine action, mediated via platelet beta-adrenoceptors. Since chronic treatment with adrenaline did not exert such an effect, the action of nicotine may, rather, be attributed to increases in endogenous noradrenaline. These results could explain varying responses of human blood platelets in smokers.
Becker
B F
BF
Physiologisches Institut, Universität München.
Terres
W
W
Kratzer
M
M
Gerlach
E
E
D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects*; D003367:Cotinine / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009538:Nicotine / Q000493:pharmacokinetics / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D009538:Nicotine; D003367:Cotinine