Abstract
Increasing evidence indicates there is a strong association between parental health during pregnancy and incidence of cardiovascular disease in adult offspring. Recently, hydrogen sulfide (H2S) has been demonstrated to be a powerful vasodilator of the placental vasculature, improving intrauterine growth restriction. In this study, we investigated whether parental hypertension induces autonomic dysfunction in male adult offspring, and the H2S mechanism underlying this autonomic dysfunction. 2-kidney-1-clip method was employed to induce parental hypertension during pregnancy and lactation in rats. Basal blood pressure (BP) and autonomic function of male offspring in adulthood was evaluated. Additionally, either maternal hypertensive dams or their male offspring after weaning were treated with H2S to determine improving effects of H2S on autonomic dysfunction. The BP was significantly increased in male offspring of renovascular hypertensive dams when compared to that in offspring of normotensive dams. The offspring of renovascular hypertensive dams also exhibited blunted baroreflex sensitivity, increased sympathetic effect and sympathetic tonus. Western blotting analysis revealed downregulation of endogenous H2S catalyzed enzyme and upregulation of angiotensin Ang II type 1 receptor (AT1R) pathway in the nucleus tractus solitarius and rostral ventrolateral medulla, two hindbrain nuclei involved in BP and autonomic regulation, in these offspring. Either prenatal or postnatal treatment with H2S improved the adverse effects. The results suggest that parental hypertension results in elevated BP and autonomic dysfunction in adult male offspring through activation of AT1R pathway and inhibition of endogenous H2S production in the brain.
Highlights
It is established that chronic hypertension during pregnancy leads to adverse consequences to both mothers and fetuses (Lykke et al, 2009)
The Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean artery pressure (MAP) were measured at 16 weeks in male offspring Compared with control group at 16 weeks, SBP, DBP and MAP in offspring of renovascular hypertensive rats were significantly increased from 113.59 ± 3.29 mmHg to 146.34 ± 10.97 mmHg, 93.82 ± 7.53 vs. 112.51 ± 8.68 mmHg, 100.41 ± 5.8 vs. 123.78 ± 8.5 mmHg P < 0.05
(2) angiotensin II receptor 1 (AT1) receptor, oxidative stress and inflammation-related protein were up regulated in male offspring of renovascular hypertensive dams
Summary
It is established that chronic hypertension during pregnancy leads to adverse consequences to both mothers and fetuses (Lykke et al, 2009). Many studies have shown that an adverse intrauterine environment, mothers with pre-eclampsia or chronic hypertension, inflammation, undernutrition, reductions in sleep during pregnancy, diabetes, and so on, results in an increased risk of cardiovascular diseases in the adult offspring (Barker, 1990; Lazdam et al, 2010; Staley et al, 2015; Wu et al, 2015). These studies indicate that sympathetic overactivation, autonomic dysfunction and inflammation may contribute to the development of hypertension in the offspring of mothers with a variety of insults during pregnancy and/or lactation. Renovascular hypertension was employed to induce secondary hypertension in parental rats
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