The Relationship Between Nocturnal Blood Pressure and Hemorrhagic Stroke in Chinese Hypertensive Patients

To study the relationship between nocturnal blood pressure (BP) variation and spontaneous intracerebral hemorrhage (ICH) among Chinese hypertensive patients and its clinical significance, the authors retrospectively screened 371 patients with primary hypertension (189 patients with ICH, 182 patients without ICH) in Shanghai and analyzed their demographics, clinical information, nocturnal blood pressure variability and medication. Compared with the control group, the levels of blood glucose, triglycerides, and creatinine were significantly increased in the ICH group, along with a marked reduction in nocturnal BP drop (P<.05). Multivariate logistic regression indicated that blood glucose, creatinine, and nocturnal mean arterial pressure were risk factors for ICH, and the magnitude of nocturnal BP drop was negatively related to the risk for ICH. There was no significant difference in the prevalence of reverse dippers between the large hematoma volume group and the small hematoma volume group (χ²=2.529, P=.112), nor among the patients taking angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers (χ²=1.981, P=.371). Reverse dipping is associated with the risk for ICH, suggesting that appropriate antihypertensive drug and chronotherapy might be effective to normalize the rhythm of abnormal circadian variation in hypertensive patients.     

Elevated Serum Uric Acid is Associated With Angiotensinogen in Obese Patients With Untreated Hypertension

This study investigated the correlation between elevated serum uric acid (SUA) and angiotensinogen in obesity patients with hypertension. A total of 162 obese and 162 nonobese men with hypertension were recruited in this study. Plasma angiotensinogen levels were measured by enzyme‐linked immunosorbent assay. Fasting insulin (FINS) was evaluated by radioimmunoassay. Compared with nonobese patients, obese patients exhibited higher levels of angiotensinogen, FINS, and homeostasis model assessment index‐insulin resistance (HOMA‐IR) (P<.001 for all). Moreover, these indexes significantly increased in obese patients in the highest tertile of SUA when compared with those in the lowest tertile of SUA (P<.001, P=.002, P=.007, respectively). In the obese group, SUA levels were significantly related to angiotensinogen, FINS, and HOMA‐IR, respectively. Furthermore, it was demonstrated that obesity × uric acid was an independent contributor to angiotensinogen (β=0.257, P<.001). In conclusion, elevated SUA is strongly related to angiotensinogen in an obesity‐dependent manner in hypertension.     

Calcium Channel Blocker Compared With Angiotensin Receptor Blocker for Patients With Hypertension: A Meta‐Analysis of Randomized Controlled Trials

To explore the clinical effects of a calcium channel blocker compared with an angiotensin II receptor blocker in hypertensive patients, the authors collected data from randomized controlled trials. The pooled outcomes were all‐cause mortality, stroke, myocardial infarction, and heart failure. Eight head‐to‐head trials enrolling 25,084 patients were included. There was no significant mortality difference in the two arms (relative risk, 0.99; 95% confidence interval, 0.91–1.07). However, calcium channel blockers were more effective in reducing stroke (relative risk, 0.87; 95% confidence interval, 0.76–0.99) and myocardial infarction incidence (relative risk, 0.86; 95% confidence interval, 0.76–0.98). There was no significant difference with heart failure incidence between the two arms but a lower trend in patients with angiotensin II receptor blockers was noted (relative risk, 1.4; 95% confidence interval, 0.99–1.98). The meta‐analysis suggested that initially use of a calcium channel blocker might be superior to an angiotensin II receptor blocker for prevention of stroke and myocardial infarction.     

Comparing human and mouse salivary glands: A practice guide for salivary researchers

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.     

Glucocorticoid receptor signaling is essential for mesoderm formation and muscle development in zebrafish

Glucocorticoid receptor (GR) signaling is thought to play a key role in embryogenesis, but its specific developmental effects remain unclear. Cortisol is the primary ligand for GR activation in teleosts, and in zebrafish (Danio rerio), the prehatch embryo content of this steroid is of maternal origin. Using early zebrafish developmental stages, we tested the hypothesis that GR signaling is critical for embryo growth and hatching. In zebrafish, maternal GR mRNA is degraded quickly, followed by zygotic synthesis of the receptor. GR protein is widely expressed throughout early development, and we were able to knockdown this protein using morpholino oligonucleotides. This led to a more than 70% reduction in mRNA abundance of matrix metalloproteinase-13 (mmp13), a glucocorticoid-responsive gene. The GR morphants displayed delayed somitogenesis, defects in somite and tail morphogenesis, reduced embryo size, and rarely survived after hatch. This correlated with altered expression of myogenic markers, including myogenin, myostatin, and muscle-specific myosin heavy chain and troponin genes. A key finding was a 70-90% reduction in the mRNA abundance of bone morphogenetic proteins (BMP), including bmp2a, bmp2b, and bmp4 in GR morphants. Bioinformatics analysis confirmed multiple putative glucocorticoid response elements upstream of these BMP genes. GR morphants displayed reduced expression of BMP-modulated genes, including eve1 and pax3. Zebrafish GR mRNA injection rescued the GR morphant phenotype and reversed the disrupted expression of BMP and myogenic genes. Our results for the first time indicate that GR signaling is essential for zebrafish muscle development, and we hypothesize a role for BMP morphogens in this process.     

Central and peripheral glucocorticoid receptors are involved in the plasma cortisol response to an acute stressor in rainbow trout

Cortisol, the primary circulating corticosteroid in teleosts, is elevated during stress following activation of the hypothalamus-pituitary-interrenal (HPI) axis. Cortisol exerts genomic effects on target tissues in part by activating glucocorticoid receptors (GR). Despite a well-established negative feedback loop involved in plasma cortisol regulation, the role of GR in the functioning of the HPI axis during stress in fish is still unclear. We used mifepristone (a GR antagonist) to suppress GR signaling in rainbow trout (Oncorhynchus mykiss) and assessed the resultant changes to HPI axis activity. We show for the first time that mifepristone caused a functional knockdown of GR by depleting protein expression 40-75%. The lower GR protein expression corresponded with a compensatory up-regulation of GR mRNA levels across tissues. Mifepristone treatment completely abolished the stressor-induced elevation in plasma cortisol and glucose levels seen in the control fish. A reduction in corticotropin-releasing factor (CRF) mRNA abundance in the hypothalamic preoptic area was also observed, suggesting that GR signaling is involved in maintaining basal CRF levels. We further characterized the effect of mifepristone treatment on the steroidogenic capacity of interrenal tissue in vitro. A marked reduction in cortisol production following adrenocorticotropic hormone stimulation of head kidney pieces was observed from mifepristone treated fish. This coincided with the suppression of steroidogenic acute regulatory protein, but not P450 side chain cleavage mRNA abundances. Overall, our results underscore a critical role for central and peripheral GR signaling in the regulation of plasma cortisol levels during stress in fish.