Alterations in prostacyclin and thromboxane formation by chronic cigarette smoke exposure: temporal relationships and whole smoke vs. gas phase.
Chronic cigarette smoke exposure in vivo causes decreased conversion of [14C]arachidonic acid (AA) to prostacyclin (PGI2) by isolated aortic tissue and increased conversion to thromboxane (TXA2) by isolated platelets from rats. Alterations in the PGI2/TXA2 balance may be part of the mechanism through which smoking increases the risk of cardiovascular disease. To study the influence of smoke exposure duration on this response, male rats were exposed daily to 10 puffs of freshly generated cigarette smoke. Animals were killed after 1, 4, 14, 28 and 57 days of smoke exposure and 3, 7, 14 and 28 days after cessation of the 57-day of smoke-exposure regimen. Elevated carboxyhemoglobin levels during the smoke-exposure sessions verified smoke (gas phase) inhalation. Statistically significant alterations in prostacyclin synthesis preceded those of thromboxane. A decrease of 20-25% (P less than 0.05) in PGI2 production from [14C]AA in isolated aortic tissue was found beginning 28 days after smoke was initiated and quickly rebounded when smoke exposure was terminated. Increased production of TXA2 from [14C]AA by isolated platelets became statistically significant (P less than 0.05) on the 57th day and returned to normal 7-14 days after cessation of smoke exposure. To determine the effect of gas phase constituents on the PGI2/TXA2 balance a second series of experiments divided male and female Sprague-Dawley rats into sham, whole smoke and gas phase groups. Gas phase was produced by passing whole smoke through a Cambridge filter to remove particulate matter. Per cent COHb averaged 1.4 for sham, 7.8 for whole smoke and 9.4 for gas phase groups.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D002263:Carboxyhemoglobin / Q000032:analysis; D004781:Environmental Exposure; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D010947:Plants, Toxic; D051381:Rats; D011919:Rats, Inbred Strains; D012906:Smoke / Q000009:adverse effects*; D013931:Thromboxanes / Q000096:biosynthesis*; D014026:Nicotiana
D012906:Smoke; D013931:Thromboxanes; D015121:6-Ketoprostaglandin F1 alpha; D009538:Nicotine; D002263:Carboxyhemoglobin; D011464:Epoprostenol