The causes of hypertension are complex and involve both genetic and environmental factors. Environment changes during fetal development have been linked to adult diseases including hypertension. Studies show that timed in utero exposure to the synthetic glucocorticoid (GC) dexamethasone (Dex) results in the development of hypertension in adult rats. Evidence suggests that in utero stress can alter patterns of gene expression, possibly a result of alterations in the topology of the genome by epigenetic markers such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). The objective of this study was to determine the effects of epigenetic regulators in the fetal programming and the development of adult hypertension. Specifically, this research examined the effects of the HDAC inhibitor valproic acid (VPA) and the DNMT inhibitor 5-aza-2′-deoxycytidine (5aza2DC) on blood pressure (BP) and gene expression in prenatal Dex-programmed rats. Data suggest that both VPA and 5aza2DC attenuated the Dex-mediated development of hypertension and restored BP to control levels. Epigenetic DNMT inhibition (DNMTi) or HDAC inhibition (HDACi) also successfully attenuated elevations in the majority of altered catecholamine (CA) enzyme expression, phenylethanolamine N-methyltransferase (PNMT) protein, and elevated epinephrine (Epi) levels in males. Although females responded to HDACi similar to males, DNMTi drove increased glucocorticoid receptor (GR) and PNMT expression and elevations in circulating Epi in females despite showing normotensive BP.

The field of cardiovascular fetal programming has emphasized the importance of the uterine environment on postnatal cardiovascular health. Studies have linked increased fetal glucocorticoid exposure, either from exogenous sources (such as dexamethasone (Dex) injections), or from maternal stress, to the development of adult cardiovascular pathologies. Although the mechanisms are not fully understood, alterations in gene expression driven by altered oxidative stress and epigenetic pathways are implicated in glucocorticoid-mediated cardiovascular programming. Antioxidants, such as the naturally occurring polyphenol epigallocatechin gallate (EGCG), or the superoxide dismutase (SOD) 4-hydroxy-TEMPO (TEMPOL), have shown promise in the prevention of cardiovascular dysfunction and programming. This study investigated maternal antioxidant administration with EGCG or TEMPOL and their ability to attenuate the fetal programming of hypertension via Dex injections in WKY rats. Results from this study indicate that, while Dex-programming increased blood pressure in male and female adult offspring, administration of EGCG or TEMPOL via maternal drinking water attenuated Dex-programmed increases in blood pressure, as well as changes in adrenal mRNA and protein levels of catecholamine biosynthetic enzymes phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), dopamine beta hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), in a sex-specific manner. Furthermore, programmed male offspring displayed reduced antioxidant glutathione peroxidase 1 (Gpx1) expression, increased superoxide dismutase 1 (SOD1) and catalase (CAT) expression, and increased pro-oxidant NADPH oxidase activator 1 (Noxa1) expression in the adrenal glands. In addition, prenatal Dex exposure alters expression of epigenetic regulators histone deacetylase (HDAC) 1, 5, 6, 7, 11, in male and HDAC7 in female offspring. These results suggest that glucocorticoids may mediate the fetal programming of hypertension via alteration of epigenetic machinery and oxidative stress pathways.

The immune system is increasingly recognized for its role in the genesis and progression of hypertension. The adrenal gland is a major site that coordinates the stress response via the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal system. Catecholamines released from the adrenal medulla function in the neuro-hormonal regulation of blood pressure and have a well-established link to hypertension. The immune system has an active role in the progression of hypertension and cytokines are powerful modulators of adrenal cell function. Adrenal medullary cells integrate neural, hormonal, and immune signals. Changes in adrenal cytokines during the progression of hypertension may promote blood pressure elevation by influencing catecholamine biosynthesis. This review highlights the potential interactions of cytokine signaling networks with those of catecholamine biosynthesis within the adrenal, and discusses the role of cytokines in the coordination of blood pressure regulation and the stress response.

To understand the economics of root aerenchyma formation in wetland plants, we investigated in detail the response of Alisma triviale to waterlogging. We hypothesized costs being associated with development of a large root air space. In three out-door pot experiments, seedlings (1 experiment) and mature plants (2 experiments) were grown under waterlogged and drained conditions for up to 2 months. Waterlogging promoted growth, and was associated with increased root porosity and decreased root density (fresh mass per volume). The increased formation of aerenchyma was associated with a higher root dry matter content for a given root density. Despite improved growth and earlier flowering, the waterlogged plants also showed signs of being constrained by the anoxic substrate, such as shallower roots, and a higher leaf dry matter content. The formation of aerenchyma was associated with costs, such as increased root dry matter content and reduced metaxylem vessel diameter. The faster growth of the seedlings under the waterlogged conditions, despite some signs of being stressed, was possibly a result of decreased requirements to allocate biomass below ground. In mature plants the increased aerenchyma allowed deeper root penetration, and ameliorated the effects of anoxia, reducing the differences in plant traits between the treatments.

BackgroundThe renal renin-angiotensin system (RAS) is physiologically important for blood pressure regulation. Altered regulation of RAS-related genes has been observed in an animal model of hypertension (spontaneously hypertensive rats – SHRs). The current understanding of certain RAS-related gene expression differences between Wistar-Kyoto rats (WKYs) and SHRs is either limited or has not been compared. The purpose of this study was to compare the regulation of key RAS-related genes in the kidneys of adult WKYs and SHRs.Material/MethodsCoronal sections were dissected through the hilus of kidneys from 16-week-old male WKYs and SHRs. RT-PCR analysis was performed for Ace, Ace2, Agt, Agtr1a, Agtr1b, Agtr2, Atp6ap2 (PRR), Mas1, Ren, Rnls, and Slc12a3 (NCC).ResultsIncreased mRNA expression was observed for Ace, Ace2, Agt, Agtr1a, Agtr1b, and Atp6ap2 in SHRs compared to WKYs. Mas1, Ren, Slc12a3, and Rnls showed no difference in expression between animal types.ConclusionsThis study shows that the upregulation of several key RAS-related genes in the kidney may account for the increased blood pressure of adult SHRs.