Prostacyclin production by the heart: effect of nicotine and carbon monoxide.
Smoking has been linked to the development and progression of atherosclerosis but the mechanism by which smoking exerts its deleterious effects remains unknown. This study was designed to examine in a systematic way the effects of nicotine and carbon monoxide on platelets, arterial walls, and the heart. Results of experiments designed to assess the effect of nicotine and carbon monoxide on the production of prostacyclin (PGI2) by the rabbit heart are reported. Animals exposed to carbon monoxide had the carboxyhemoglobin raised to at least 12% by breathing an atmosphere enriched with carbon monoxide. Nicotine was infused at 50 micrograms/kg/hr for 1 week. Nicotine was measured by gas/liquid chromatography. PGI2 was measured by radioimmunoassay of 6-keto-PGF1 alpha, and its biologic activity was assessed by inhibition of platelet aggregation. Nicotine is concentrated in the heart and blood vessel wall and causes a statistically significant reduction in PGI2 production. Carbon monoxide raised PGI2 production significantly in all chambers, and the combination of nicotine and carbon monoxide further raised PGI2 production. The difference between the effects of nitrogen and carbon monoxide alone and nitrogen and a combination of nitrogen and carbon monoxide was significant in all chambers. It is hypothesized that nicotine exerts a direct metabolic effect in lowering PGI2 production. Carbon monoxide may make the endothelial cell relatively hypoxic, a powerful stimulus of PGI2 production, or less likely exert a direct toxic effect on the endothelial cell.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000494:pharmacology*; D002263:Carboxyhemoglobin / Q000032:analysis; D002849:Chromatography, Gas; D011464:Epoprostenol / Q000032:analysis / Q000096:biosynthesis*; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009538:Nicotine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D011863:Radioimmunoassay
D015121:6-Ketoprostaglandin F1 alpha; D009538:Nicotine; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D011464:Epoprostenol