Experimental atherosclerosis: effects of oestrogen and atherosclerosis on thromboxane and prostacyclin formation

Abstract

We evaluated the effect of oestrogen and experimental atherosclerosis on the in vivo formation of thromboxane and prostacyclin in rabbits. Twenty-four New Zealand White rabbits were divided into four groups. One group received control diet, one group received control diet and oestrogen, one group received control diet supplemented with 1% cholesterol and one group received cholesterol supplemented diet and oestrogen during 3 months. The in vivo formation of thromboxane and prostacyclin were measured as 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha in urine by gas chromatography/mass spectrometry. All rabbits on cholesterol diet became hypercholesterolaemic and developed atherosclerosis. As in previous experiments cholesterol and oestrogen-treated rabbits had only minor atherosclerosis compared to purely cholesterol-fed rabbits. The in vivo production of thromboxane in oestrogen-treated rabbits decreased from 1641 +/- 162 pg mg-1 creatinine pretreatment to 808 +/- 92 pg mg-1 creatine at 12 weeks (P = 0.0001). In contrast, the in vivo production of prostacyclin increased during oestrogen treatment (P = 0.0027). The in vivo production of prostacyclin decreased during pure cholesterol feeding without oestrogen 1384 +/- 219 pg mg-1 creatinine to 702 +/- 142 pg mg-1 creatinine (P = 0.0091). The ratio of in vivo prostacyclin to thromboxane formation increased 2-3-fold during oestrogen therapy (P = 0.0007).(ABSTRACT TRUNCATED AT 250 WORDS)