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-PGFlx in urine by gas chromatography/mass spectro-metry. All rabbits on cholesterol diet became hypercholes-terolaemic 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 pretreat-ment 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). In summary the study shows a pronounced reduction in the in vivo thromboxane formation and an increase in the ratio of prostacyclin/thromboxane production during oestrogen therapy. In parallel with this we found in this experiment, as well as in other experiments, a drastic reduction in atherosclerotic involvement during oestrogen therapy. These putative favourable changes in prostanoid formation during oestrogen treatment could add further positive actions of oestrogen on atherosclerosis in addition to previously described reductions in atherogenic lipopro-teins and increases in high density lipoprotein cholesterol.

This publication has 22 references indexed in Scilit: