Adaptaciones hemodinámicas a la gestación en ratas con hipertensión inducida por alteración de la nefrogénesisefectos de una ingesta crónica de grasa

Résumé

Pregnancy is a dynamic process associated with important structural and physiological adaptations in the maternal organism. Most of the studies that analyze hemodynamic changes throughout pregnancy in rats have used invasive techniques and/or have focused on an isolated gestational stage. Therefore, the first objective of the present doctoral thesis has been to evaluate cardiac, renal, and uterine hemodynamics, and to determine blood pressure changes throughout pregnancy in rats, using non-invasive methods such as Doppler ultrasound. The results obtained indicate that pregnant rats respond to pregnancy in a similar way than pregnant women. Based on this, different mechanisms have been proposed to contribute to these hemodynamic adaptations of the maternal organism to pregnancy, among which is the heme-oxygenase (HO) system. However, until now it remains unknown whether the contribution of the HO system regulating blood pressure during pregnancy is mediated by its actions remodeling the spiral arteries and/or its effects on uteroplacental hemodynamics. Thus, the second objective of the present doctoral thesis has been to study the contribution of the HO system to the adaptations of the uteroplacental circulation to pregnancy, and its relationship with the control of blood pressure. To do this, virgin and pregnant rats were injected with an HO inhibitor or vehicle, and blood pressure was determined before and after treatment. Uterine flow and remodeling of the spiral arteries were assessed at mid and late gestation. The data obtained indicate that the HO system contributes to the adaptation of the uteroplacental circulation and the regulation of blood pressure at the end of pregnancy. Although most women adapt normally to pregnancy, there are several risk factors, such as overweight or maternal kidney disease, which can lead to complications during pregnancy. However, there are no studies that have analyzed the possible hemodynamic alterations in overweight women or with reduced number of nephrons from the perinatal stage during pregnancy. Therefore, the third objective of the present doctoral thesis has been to analyze the hemodynamic response to pregnancy in overweight rats induced by chronic fat intake from an early age; and the fourth objective has been to determine whether the reduced number of nephrons from the perinatal stage alters the hemodynamic response to pregnancy, and may contribute to the development of a similar syndrome than human preeclampsia. With all these antecedents, the last objective of the present doctoral thesis has been to determine whether a high fat intake from early age enhances the negative effects of the reduction of nephrons from the perinatal stage on the hemodynamic response to pregnancy, and whether it increases the predisposition to develop a similar syndrome than human preeclampsia. To achieve these objectives, three experimental groups of pregnant rats were used: DAG (fed a high-fat diet from the perinatal stage); ARA (with reduced number of nephrons) and ARA-DAG (with reduced number of nephrons and fed a high fat intake from the perinatal stage). Cardiac, renal, and uterine hemodynamics were assessed in all of them; and blood pressure changes throughout pregnancy were determined using noninvasive methods. The results obtained suggest that overweight or nephron deficiency from the perinatal stage induce moderate alterations in the hemodynamic response to pregnancy and the coexistence of both can enhance these alterations becoming a risk factor for the appearance of severe gestational complications.