Kurzfassung

The current antihypertensive therapies are generally effective and well tolerated by patients. However, no optimal therapy is available for patients with a family history of severe, therapy-resistant hypertension or patients with placenta insufficiency, whose children are at higher risk to develop hypertension in adult life. For these two groups of patients, maternal treatments may represent a potential therapy option. The organic nitrate pentaerythritol tetranitrate (PETN) shows no...The current antihypertensive therapies are generally effective and well tolerated by patients. However, no optimal therapy is available for patients with a family history of severe, therapy-resistant hypertension or patients with placenta insufficiency, whose children are at higher risk to develop hypertension in adult life. For these two groups of patients, maternal treatments may represent a potential therapy option. The organic nitrate pentaerythritol tetranitrate (PETN) shows no reproductive toxicity, developmental toxicity or carcinogenicity in animal studies and reduces pregnancy complications in patients with abnormal placenta perfusion. Spontaneously hypertensive rats (SHR) are a rat model of essential hypertension. Our recent study has demonstrated that treatment of SHR during pregnancy and lactation periods with PETN led to a persistent blood pressure reduction in the female but not male offspring. In the present research proposal, we plan to study the molecular mechanisms underlying the blood pressure-programming effect of maternal treatments, including (i) epigenetic modifications induced by maternal PETN treatment; (ii) molecular mechanisms responsible for the gender-specific effect; (iii) relative importance of the treatment periods (pregnancy versus lactation); and (iv) molecular mechanisms leading to the epigenetic changes. The long-term objective of our proposal is to provide molecular information for the development of maternal treatments (PETN and other compounds) as novel preventive and therapeutic approaches.» weiterlesen» einklappen