effect of calcium antagonists on whole blood serotonin and platelet serotonin during pre-eclampsia

ABSTRACT

The purpose of this study was to assess the effect of calcium antagonists nifedipine and verapamil on blood pressure levels and the level of serotonin in both whole blood and platelets in 6 pregnant women with mild pre-eclampsia and 8 pregnant women with moderate pre-eclampsia treated with 10 mg oral dose nifedipine twice daily, while 5 pre-eclampsia pre-eclamptic women in each mild and moderate cases treated with 40 mg verapamil three times daily. The women received their specific treatment until the day of delivery. Data analysis revealed a significant decrease in systolic, diasrolic and mean arterial blood pressure in each treatment regimen compared with pre-treatment values in both mild and moderate cases. Considering whole blood 5-HT, administration of both calcium antagonists causes a significant decrease in the level of whole blood 5-HT in mild pre-eclampsia after 3- days treatment; while in moderate case there is a significant decrease after 3-days treatment with nifedipine and 6-days treatment after verapamil. Platelet serotonin level was significantly increased in mild case after 3-days of both treatments; while in moderate case, platelet serotonin level was increased after 3-days treatment with nifedipine and 6-days treatment with verapamil as compared to pre- treatment level. These observations suggest that calcium antagonists may be effective in reducing elevated blood pressure in pre-eclampsia patients and that serotonin may play a role in the pathogenesis of pre -eclampsia. Serotonin is widely distributed in nature being found in plants and animals. In human, over 90% of the serotonin is found in enterochromaffin cell in the G.I.T. The overflowing of 5-HT from cells into the blood is removed actively by the liver and the endothelium, specially in the lung. The 5-HT taken up by the endothelial cells is destroyed enzymatically by mono-amine oxidase. Most of the 5-HT escaping hepatic and pulmonary metabolism is taken up by the platelets. Serotonin activates human blood platelets by combining with specific receptors on the membrane, seems to be of the 5-HT2-type [Leysen etal., 1982]. 5-HT; receptors type also identified on vascular smooth muscle and bronchial smooth muscle, their stimulation provoked smooth muscle contraction [Vanhoutte et al., 1983], which also suggest that serotonin in hypertensive human and animal play a role in the maintenance of the chronic increase in peripheral resistance. Pre-eclampsia is associated with the increased maternal placental Vascular resistance and elevated blood pressure has been considered as a compensatory to maintain placental perfusion. Therefore antihypertensive treatment in these patients should cause uterine vasodilatation in order to avoid diversion of the placental circulation. Calcium channel blockers of the dihydropyridine group [nifedipine] characterized by their ability to influence transmembrane calcium influx. These are clinically useful peripheral vaso dilators effects and seen effective in lowering maternal Mood pressure in pre-eclampsia [Constantin et al., 1987; Barton etal., 1990]. In 1993, Lechner demonstrated an excellent uterus-relaxing properties of verapamil in addition to their efficacy as hypotensive agents in the treatment of pre-eclampsia