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.

Notable shifts from 2011 included NPs' increased familiarity with American Diabetes Association (ADA) guidelines; FPs, IMs, NPs, and PAs continued comfort with prescribing long-acting basal insulin but less with basal-bolus, Neutral Protamine Hagedorn insulin alone, or human premixed insulin; increased pharmacists' comfort in discussing long-acting basal insulin; increased likelihood that FPs will refer patients with recurrent hypoglycemia unable to achieve target glycated hemoglobin level to an ENDO; and continued incorporation of insulin and incretins into treatment regimens. The trends suggest gaps in perception, knowledge, and management practices to be addressed by education. Most HCPs lack confidence in using insulin regimens more complex than long-acting insulin alone. All providers need education on T2DM management guidelines, differences between GLP-1 agonists and DPP-4 inhibitors, and how to intensify therapy for patients not reaching goal blood glycemic level with use of multiple agents. Pharmacists might benefit from education on glycemic treatment goals.

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.

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.

Assessment of habitat suitability provides natural resource managers with insights on the quality and spatial distribution of habitat for wildlife species. However, habitat suitability models only provide information on current habitat parameters, and do not consider changes in habitat due to forest succession and disturbances. Habitat potential models have been developed by identifying habitat types and their successional trajectories to provide insights on how landscapes change with time. We developed habitat suitability index (HSI) models and habitat potential models for elk (Cervus elaphus nelsoni) on public and private lands within the Michigan elk range (1,220 km2) in northeastern lower Michigan, USA. Our objective was to demonstrate how integration of habitat suitability and habitat potential models can provide spatiotemporal insights on wildlife habitat. When constructing public‐lands models, we used state forest compartment‐inventory data to identify cover types important to elk, and assigned suitability values (0 = low, 1 = high) to each cover type for elk life requisites (i.e., spring food, winter food, winter thermal cover). Additionally, we modified suitability values based on stand conditions acquired from state forest inventory records (e.g., stand size, percent canopy closure, age of aspen [Populus spp.]). For our private‐lands models, we used satellite imagery to classify cover types and assigned suitability values to cover types for each elk life requisite, and modified values based on percent canopy closure for winter thermal cover. Elk habitat potential was modeled by delineating habitat types by overlaying digital spatial data layers (soils, land‐type associations, vegetation) and identifying successional trajectories using habitat classification guides and literature. We assigned suitability values to each habitat type for life requisites at early to late successional stages. The highest suitability value of each habitat type's successional stage determined the habitat potential for each habitat type. Our winter thermal cover HSI model indicated several large areas (5–13 km2) of high suitability (i.e., lowland conifers) in the southern third of our study area. Our winter food HSI model indicated a heterogeneous arrangement of high suitability areas (hardwoods, upland conifers, aspen) throughout our study area. Our spring food HSI model indicated few areas of high suitability (openings) primarily on private lands. Our habitat potential models indicated high potential for each elk life requisite across the elk range. Comparisons between current elk habitat suitability and habitat potential identify key areas where managers can maximize management efforts for elk in Michigan. Areas determined to have high habitat potential (e.g., mature aspen stands) may become focus areas if they currently have low habitat suitability. Conversely, managers can avoid committing resources to areas with low habitat potential. Integrating habitat suitability and potential models provides insights on how w...