Prostacyclin and thromboxane formation following chronic exposure to cigarette smoke condensate administered via osmotic pumps in rats. A method for chronic administration of particulates of whole smoke.
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 PGL2/TXA2 balance may be part of the mechanism by which smoking increases the risk of cardiovascular disease. In order to ascertain whether the particulate phase of whole smoke alone could cause these changes, rats were administered smoke condensate in propylene glycol for 56 days via two Alzet (2ML4) osmotic pumps. Pumps containing vehicle, low dose (150 micrograms/hr) or high dose (300 micrograms/hr) condensate were implanted s.c. dorsal to the thoracic vertebrae in male Sprague-Dawley rats. Three-quarters of the condensate-treated rats developed fibrin cysts encapsulating the pumps. Cysts were not seen in vehicle-treated rats. Residual pump contents were weighed and analyzed by GLC to ensure condensate delivery. No significant difference in weight gain patterns between sham-operated and treatment groups were observed. Vehicle had no effect on aortic PGI2 or platelet TXA2 formation compared to sham. Low-dose condensate was without effect on PGI2/TXA2 formation. In high-dose condensate-treated rats, PGI2 and TXA2 formation were 84% and 136%, respectively, of the vehicle control (n.s.). Pump encapsulation may be a limiting factor in the administration of complex particulate suspensions.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002849:Chromatography, Gas; D003367:Cotinine / Q000652:urine; D011464:Epoprostenol / Q000378:metabolism*; D008297:Male; D009995:Osmosis; D051381:Rats; D011919:Rats, Inbred Strains; D012907:Smoking / Q000378:metabolism*; D013931:Thromboxanes / Q000378:metabolism*; D013997:Time Factors
D013931:Thromboxanes; D011464:Epoprostenol; D003367:Cotinine