COTININE MODULATES THE CARDIOVASCULAR EFFECTS OF NICOTINE

Although nicotine exerts a sympatho-excitatory effect, chronic cigaret te smokers do not generally suffer from arterial hypertension. It is p roposed that cotinine, the major metabolite of nicotine, may be implic ated in this paradox. This hypothesis was evaluated by studying arteri al blood pressure and isolated aorta of rabbits. At high dose (100 mg kg(-1) i.v.), cotinine caused a rapid and lasting hypertension. Cotini ne pre-treatment completely blocked the hypertensive action of high do se nicotine (0.125 mg kg(-1) i.v.). Furthermore, cotinine, relaxed iso lated rabbit aorta and antagonised the contractile effects of nicotine and noradrenaline in a noncompetitive fashion. These observations sup port the modulatory action of cotinine on the contractile and presser effects of nicotine.