Abstract

ObjectiveNumerous findings have demonstrated a strong association between parental health during pregnancy and cardiovascular disease in adult offspring. This study investigated whether sensitivity to angiotensin II (Ang II) is enhanced in offspring of renovascular hypertensive animals and whether hydrogen sulfide (H2S) can attenuate the increased response to Ang II in offspring.MethodThe systolic blood pressure (SBP) was measured by non-invasive tail-cuff plethysmograpy every two weeks in all offspring from 8 to 16 weeks. After intracerebroventricular microinjection of Ang II in the offspring, blood pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded to test the response to Ang II in the offspring. Western blot analysis was used to examine the protein expression of AT1R, AT1R-associated protein (ATRAP), Nox2, p67phox, and nitrotyrosine in the nucleus tractus solitarii (NTS).ResultsThe SBP in the offspring of hypertensive rats were significantly higher than that in control group, and the above effects were significantly improved by prenatal or postnatal administration of H2S. Intralateroventricular microinjection of Ang II induced greater sympathetic responses in offspring of hypertensive rats than control group. The expression of AT1R and oxidative stress-related protein was increased, whereas that of ATRAP was decreased in the NTS in offspring of hypertensive rats. Exogenous administration of H2S prenatally or postnatally improved the above effects.ConclusionPrenatal or postnatal administration of H2S attenuated AngII-induced sympathetic excitation in offspring of hypertensive rats, which may occur by modulating the balance between AT1R and ATRAP and downregulating oxidative stress-related protein expression in the NTS.

Highlights

  • Increasing evidence has shown that an adverse intrauterine environment, such as in mothers with hypertension and diabetes, increases the risk of cardiovascular diseases in adult offspring (Barker and Osmond, 1986; Kobori et al, 2007; Samuelsson et al, 2013)

  • In female offspring of renovascular hypertensive dams, the systolic blood pressure (SBP) significantly elevated when compared with control from 8 to 16 weeks

  • We have found that SBP in offspring of renovascular hypertensive significantly increased from 8 to 16 weeks; with intracerebroventricular infusion of Ang II, the parameters MAP, HR and RSNA were greater in offspring of parents with than without Renovascular hypertension (RVH)

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Summary

Introduction

Increasing evidence has shown that an adverse intrauterine environment, such as in mothers with hypertension and diabetes, increases the risk of cardiovascular diseases in adult offspring (Barker and Osmond, 1986; Kobori et al, 2007; Samuelsson et al, 2013). In women with preeclampsia in pregnancy, their children tend to have cardiovascular disease later in life (Bokslag et al, 2016). A similar study reported that children of women with preeclampsia showed increased risk of stroke in adulthood (Kajantie et al, 2009). In pregnant women with diabetes, the probability of cardiovascular diseases was increased in their adult offspring (Ma et al, 2015). Nicotine exposure during pregnancy leads to increased risk of hypertension and metabolic disorders in adult offspring (Xiao et al, 2008; Somm et al, 2009). Early intervention can prevent the development of adult hypertension (Koeners et al, 2010; Koeners et al, 2011)

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