Modulazione della funzione vascolare in gravidanza e preeclampsia

In preeclampia proved the presence of a defect in the synthesis of angiogenic factors along with metabolic risk factors that could also lead to disjointed development of the disease.Experimental data suggest that eicosanoids derived from arachidonic acid metabolism by cytochrome P450 (CYP) involved in regulating blood pressure and renal sodium excretion, may have a role in abnormal placental vascularization and development of hypertension and renal dysfunction in pregnancy. We studied 19 women in a cross-sectional study involving women with pregnancy complicated by preeclampsia (hypertension after the 20th week of gestation and proteinuria> 300 mg / day) compared with 33 women with physiological pregnancy at delivery and 20 non-pregnant women.The three groups were matched for age (21-45 years), BMI pregravidico (all preeclamptic women <21) and absence of metabolic risk factors (obesity, diabetes mellitus, preexisting hypertension). It 'was analyzed by mass spectrometry eicosaepossitrienoici plasma concentration of acids (EETs) and their metabolites (DHETs measured in plasma and urine) along with the plasma and urinary 20-idrossieicosatetraenoico acid (20-HETE). The analysis of data concerning the eicosanoids derived from arachidonic acid metabolism via cytochrome P450 showed a statistically significant increase in concentration of plasma EETs in normotensive pregnancy (median 9.92, range 6.34-25.15) compared to control non-pregnant (median 7.33, range 3.73-10.26, n = 32) and even more evident in pregnancies complicated with preeclampsia (median 10.89, range 5.97-48.04, n = 19) compared with non pregnant controls (median 7.33, range 3.73-10.26, n = 20 p <0.0001 vs. controls and preeclampsia pregnancy vs controls) without significant changes in plasma DHETs. The urinary excretion of DHETs is greater in pregnancy compared to normotensive non-pregnant condition, and lower in case of preeclampsia (p <0.05). The figure confirms if corrected for creatinine and is indicative of possible reduced activity of epoxide hydrolase during pregnancy. The concentration of plasma 20-HETE in normotensive pregnancy (median 0.38, range 0.18-0.74, n = 32) is lower than non- pregnant women (median 0.52, range 0.31-0.76, n = 20, p <0.01) while no differences than that seen in preeclampsia (median 0.4, range 0.13-1.1, n = 19). Regarding the 'urinary excretion of 20-HETE, can spy intrarenal production, the three groups have a homogeneous behavior also correcting the data for the renal excretion of creatinine. In a second study we compared the plasma concentrations of EETs, and 20-HETE DHETs obtained from maternal blood and from umbilical cord in 7 patients with preeclampsia, 16 women with physiological pregnancy and 16 nonpregnant healthy controls, all matched for age and BMI pregravidico. The group of women with preeclampsia gave birth at earlier gestational age (p <0.001), children weighing less (p <0.001) and also with placentas weighing less (p <0.001) versus uncomplicated pregnancy. Both groups also differed in values cretininemia and uric acid significantly higher in the preeclampsia group (p <0.01). The levels of EETs, DHETs and 20-DHETs plasma and erythrocytes in blood of the umbilical vein that drains the placenta were significantly higher than that observed in plasma and erythrocytes of mothers (brachial vein). This finding is particularly evident for total EETs derived from fetal red blood cells, that were found to be approximately 3 times higher than maternal (MW p <0.001) and the difference is even more evident if one considers the plasma EETs (the fetal circulation around 4 times higher than in the maternal one (MW p<0.001). It was observed a positive correlation between fetal blood pCO2 and total plasma concentration of EETs whereas both globally pregnant (r = 0.52, p <0.01) and considering separately the group of women with pregnancies complicated by hypertension (r = 0.76, p <0.05). In conclusion, our work suggests a role of arachidonic acid derivatives via CYP modulation of hemodynamics in pregnancy and preeclampsia. In pregnancies complicated by preeclampsia, the increase in EETs, stimulated from inflammation, hypoxia and oxidative stress, could be a protective factor for pregnancy and fetal well-being opposed to the increase in peripheral vascular resistance, arterial stiffness and blood pressure on one side and the other all'ipoperfusione placenta and fetal hypoxia. The decline of epossido-hydrolase may partially explain the increase of plasma EETs and reduced renal excretion of the DHETs preeclampsia. Fetal red blood cells are the source of production of EETs. The increase in the generation of EETs (vasodilator, anti-inflammatory and pro-angiogenic) may modulate the fetal-placental hemodynamics, especially in hypoxic conditions (pCO2-correlation EETs).