SMOKE-DERIVED NITRIC-OXIDE AND VASCULAR PROSTACYCLIN ARE UNABLE TO COUNTERACT THE PLATELET EFFECT OF INCREASED THROMBOXANE FORMATION IN HEALTHY FEMALE SMOKERS

The incidence of cigarette smoking tends to be higher in women, justif ying directed studies on smoke-related mechanisms of cardiovascular di sorder in females. Platelet activity plays an important etiological ro le in several settings of cardiovascular disease. Cigarette smoking fa cilitates platelet formation of proaggregatory thromboxane A(2), Howev er, cigarette smoke contains nitric oxide (NO), which has antiplatelet activity. Furthermore, the formation of anti-aggregatory prostacyclin (PGI(2)) may be higher in smokers than in non-smokers. Hence, the con certed action of NO and PGI(2) on platelet activity in smoking females is important to elucidate. The metabolites of TxA(2), NO, and PGI(2), as well as cyclic guanosine 3':5'-monophosphate (cGMP; second messeng er for NO in the platelets) and cyclic adenosine 3':5'-monophosphate ( cAMP; second messenger for PGI(2) in the platelets), were analysed in 23 healthy female smokers (daily consumption 11-20 cigarettes per day) and in 26 matched non-smokers. The urinary excretion of 2,3-dinor TxB (2) (metabolite of TxA(2)) was considerably higher in smokers than in non-smokers (177 vs. 72 pg/mg creatinine, respectively; P<0.001). Plas ma and urinary levels of nitrate (metabolite of inhaled NO) did not di ffer between the groups. Plasma and urinary cGMP were slightly increas ed (252 vs. 193 nmol/L; P<0.05 and 0.63 vs. 0.51 mu mol/24 h; P<0.05, respectively) in smokers compared to non-smokers, while platelet cGMP was lower in smokers than in non-smokers (81 vs. 10.3 pmol/10(6) plate lets, respectively; P<0.05). The urinary excretion of 2,3-dinor-6-keto -PGF(1a) (metabolite of PGI(2)) did not differ between the groups. Pla telet or urinary cAMP did not differ between the groups either, while plasma cAMP was lower in smokers than in non-smokers (19.2 vs. 26.2 nm ol/l, respectively; P<0.001). In healthy female smokers NO is not abso rbed from the inhaled smoke, and endothelial PGI(2) formation is not e nhanced to counterbalance the increased platelet formation of proaggre gatory TxA(2).