Kurzfassung

Both genetic and epigenetic mechanisms contribute to the pathogenesis of hypertension. Therefore, epigenetic drug intervention may represent a novel preventive and therapeutic approach. In the present research project, we plan to treat spontaneously hypertensive rats (a rat model of essential hypertension) during pregnancy and lactation periods with pentaerythritol tetranitrate (PETN) and to study the effect of such a treatment on the blood pressure development in the next generation. PETN is...Both genetic and epigenetic mechanisms contribute to the pathogenesis of hypertension. Therefore, epigenetic drug intervention may represent a novel preventive and therapeutic approach. In the present research project, we plan to treat spontaneously hypertensive rats (a rat model of essential hypertension) during pregnancy and lactation periods with pentaerythritol tetranitrate (PETN) and to study the effect of such a treatment on the blood pressure development in the next generation. PETN is an organic nitrate currently in clinical use for angina pectoris. The drug is devoid of nitrate tolerance and shows no reproductive or developmental toxicity in animal studies. Recently, PETN has been shown to reduce the risk of intrauterine growth restriction and/or perinatal death, and the risk for preterm birth in women with abnormal placental perfusion. We propose that maternal PETN treatment may have a long-lasting, blood pressure-lowering effect in the next generation resulting from epigenetic modifications. PETN is a nitric oxide (NO) donor with antioxidant effects. Because NO and reactive oxygen species are known to regulate epigenetic enzymes through a number of pathways, we propose that the blood pressure-programming effect of PETN may result from NO- and redox-dependent epigenetic modifications that occurs during the in-utero and perinatal periods. » weiterlesen» einklappen