Determining Risk Factors for Triple Whammy Acute Kidney Injury

Concurrent use of a diuretic, a renin-angiotensin system (RAS) inhibitor, and a non-steroidal anti-inflammatory drug (NSAID) significantly increases the risk of acute kidney injury (AKI). This phenomenon is known as "triple whammy". Diuretics and RAS inhibitors, such as an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, are often prescribed in tandem for the treatment of hypertension, whereas some NSAIDs, such as ibuprofen, are available over the counter. As such, concurrent treatment with all three drugs is common. The goals of this study are to better understand the mechanisms underlying the development of triple whammy AKI and to identify physiological factors that may increase an individual's susceptibility. To accomplish these goals, we utilize computational models of long-term blood pressure regulation. These models include variables describing the heart and circulation, kidney function, sodium and water reabsorption in the nephron and the RAS and are parameterized separately for men and women. Hypertension is modeled as overactive renal sympathetic nervous activity. Model simulations suggest that individual variations in water intake, the myogenic response, and drug sensitivity may predispose patients with hypertension to develop triple whammy-induced AKI.

The Role of Social Context in Physiological and Psychological Restoration in a Forest: Case Study of a Guided Forest Therapy Program in Taiwan

Existing studies have demonstrated the restorative benefits of being in forests. However, most studies have designed participants to engage individually in forest walking and viewing, which neglects the social aspect of conversation. Researchers suggested that social context should be studied in order to have a better understanding how forests foster human health. To this end, we examined the role of social context using three types of forest therapy programs: a guided program, a self-guided program, and a walk alone program. A between-subject, pretest–posttest field experimental design was employed to evaluate restorative effects by measuring the physiological responses and mood states incurred in different forest therapy programs. Our findings showed, that the walk alone group exhibited a significant systolic blood pressure decrease and a significant increase in sympathetic nervous activity; the self-guided group showed a significant increase in heart rate values and significant decreases in systolic blood pressure and diastolic blood pressure; and the guided group revealed a significant decrease in systolic blood pressure. Further, the three forest therapy programs had positive effects on improving mood states, except a nonsignificant vigor–activity increase in the walk alone group. The three programs did not exhibit significant differences in changes of restorative benefits in physiological and psychological measures except for a significant difference in changes in sympathetic nervous activity between the walk alone group and guided group. The results showed the restorative benefits of forest therapy are apparent regardless of the program type. The management team should continue promoting forest therapy for public health by providing different types of forest therapy programs and experiences.

Differential Antihypertensive Effects of Oral Doses of Acetylcholine between Spontaneously Hypertensive Rats and Normotensive Rats

Acetylcholine (ACh) is a novel antihypertensive food component. Here, we demonstrate the differential effects of oral ACh on high and normal blood pressure in rats. Spontaneously hypertensive rats (SHRs) and Wistar–Kyoto (WKY) rats were administered ACh orally. The blood pressure and heart rate of SHRs were significantly lowered with ACh doses of 10−5 and 10−3 mol/kg body weight (b.w.), and the urinary catecholamine levels were significantly decreased with 10−3 mol/kg b.w. In contrast, oral ACh administration had no effect on WKY rats. This difference was likely caused by differences in sympathetic nervous activity and the baroreflex between strains. Comparison of gene sequences between the two strains revealed Chga mutations, suggesting that changes in the expression of chromogranin A might be involved in the baroreflex in SHRs. Oral ACh had an antihypertensive effect under hypertension but not normotension, indicating that this may be used safely to prevent hypertension.

Abstract P157: Altered ERK-mediated Control Of AgRP And Metabolic Rate During Obesity

Adaptation of resting metabolic rate (RMR) contributes to the maintenance of human obesity, yet the control of RMR - and how this system changes during obesity - remains poorly defined. Leptin normally suppresses Agouti-related peptide (AgRP) expression in the arcuate nucleus of the hypothalamus (ARC) to disinhibit melanocortin-mediated stimulation of RMR. Leptin stimulates ERK signaling in the ARC (a known suppressor of AgRP), and the inhibition of ARC ERK attenuates thermogenic sympathetic nervous activity responses to leptin. Diet-induced obesity (DIO) increases leptin, but paradoxically exaggerates ARC AgRP expression and causes RMR adaptation. Thus, we hypothesize that leptin increases ERK signaling in AgRP cells, to reduce AgRP and thereby ultimately increase RMR, but that this signaling mechanism becomes dysfunctional during DIO. Leptin application to GT1-7 cells (a model of AgRP neurons) increased pERK/ERK ratio (1 uM, 15 min leptin n=3, 2.9-fold of vehicle n=2, p<0.05). In chow-fed adult mice, leptin injection caused an increase in ARC pERK/ERK ratio (2 ug/g ip 30 min leptin n=11, +43.8% vs saline n=9, p<0.05) without affecting total ERK levels (normalized to beta-actin). DIO caused increases in endogenous plasma leptin and an increase in ARC pERK/ERK ratio (HFD n=5, +54.4% vs chow n=4, p<0.05) without affecting total ERK levels - yet, canonical transcriptomic effects of ERK (ie, suppression of AgRP) were lost. Finally, reanalysis of our published single-nucleus RNAsequencing dataset describing the transcriptome of ARC after DIO demonstrates loss of canonical effects of increased ERK signaling specifically within the AgRP cell type. Together, these findings indicate that although DIO is associated with expected increases in ERK activation in AgRP neurons and the ARC, the consequences of ERK signaling are attenuated. We therefore hypothesize that DIO results in RMR adaptation through changes in signaling mechanisms that link ERK to its downstream targets, such as AgRP. Ongoing studies are focused on the development of novel animal models with tamoxifen-dependent conditional deletion of ERK within the adult AgRP neuron, to test whether loss of ERK signaling is sufficient to explain changes in ERK/AgRP/RMR control during DIO.

Effects of Aroma Essential Oil Inhalation on Autonomic Nerve System Response, Electroencephalogram and Concentration

Purpose: This study was an experimental research study to examine the effects of aroma essential oil inhalation on autonomic nerve system response, electroencephalogram and concentration.Methods: The participants were 92 healthy adults: 32 in the experimental group, 30 in the placebo group, and 30 in the control group. In the experimental group, lemon and rosemary oil were mixed in a ratio of 4: 1, and 0.1 ml was dropped on gauze and then naturally inhaled for a total of 30 minutes. The application for the placebo group was 0.9% saline solution, and for the control group, no treatment. To determine the effects, the autonomic nervous system response was measured by applying Canopy 9 Plus 4.0 before the experiment and at 10, 20, and 30 minutes after the experimental application, and an electroencephalogram was taken using QEEG-8. The computerized neurocognitive function test for measuring concentration was given before the experiment and at 30 minutes after the treatment.Results: There were no significant differences in the homogeneity tests for general characteristics and for the dependent variables prior to the experiment. There was a significant difference in sympathetic nervous activity between the experimental group, placebo group, and control group (F=3.78, p=.027), and the experimental group had higher sympathetic nervous activity than the control group. There was no statistically significant difference on the electroencephalogram between the ⍺ and beta waves of the three groups. The Stroop Color-Word interference test (color) of the three groups for concentration measurement was significantly different between pre test and at 30 minutes after the treatment (F=7.40, p=.001), and the score for the experimental group increased compared to the control group.Conclusion: The findings showed that the inhalation of aroma essential oil activated the sympathetic nervous system and partially increased the level of concentration.

Fifty years of research on the brain renin–angiotensin system: what have we learned?

Although the existence of a brain renin–angiotensin system (RAS) had been proposed five decades ago, we still struggle to understand how it functions. The main reason for this is the virtual lack of renin at brain tissue sites. Moreover, although renin’s substrate, angiotensinogen, appears to be synthesized locally in the brain, brain angiotensin (Ang) II disappeared after selective silencing of hepatic angiotensinogen. This implies that brain Ang generation depends on hepatic angiotensinogen after all. Rodrigues et al. (Clin Sci (Lond) (2021) 135:1353–1367) generated a transgenic mouse model overexpressing full-length rat angiotensinogen in astrocytes, and observed massively elevated brain Ang II levels, increased sympathetic nervous activity and vasopressin, and up-regulated erythropoiesis. Yet, blood pressure and kidney function remained unaltered, and surprisingly no other Ang metabolites occurred in the brain. Circulating renin was suppressed. This commentary critically discusses these findings, concluding that apparently in the brain, overexpressed angiotensinogen can be cleaved by an unidentified non-renin enzyme, yielding Ang II directly, which then binds to Ang receptors, allowing no metabolism by angiotensinases like ACE2 and aminopeptidase A. Future studies should now unravel the identity of this non-renin enzyme, and determine whether it also contributes to Ang II generation at brain tissue sites in wildtype animals. Such studies should also re-evaluate the concept that Ang-(1-7) and Ang III, generated by ACE2 and aminopeptidase A, respectively, have important functions in the brain.

Arterial Hypertension: Individual Therapeutic Approaches—From DNA Sequencing to Gender Differentiation and New Therapeutic Targets

The aim of this paper is to provide an accurate overview regarding the current recommended approach for antihypertensive treatment. The importance of DNA sequencing in understanding the complex implication of genetics in hypertension could represent an important step in understanding antihypertensive treatment as well as in developing new medical strategies. Despite a pool of data from studies regarding cardiovascular risk factors emphasizing a worse prognosis for female patients rather than male patients, there are also results indicating that women are more likely to be predisposed to the use of antihypertensive medication and less likely to develop uncontrolled hypertension. Moreover, lower systolic blood pressure values are associated with increased cardiovascular risk in women compared to men. The prevalence, awareness and, most importantly, treatment of hypertension is variable in male and female patients, since the mechanisms responsible for this pathology may be different and closely related to gender factors such as the renin–angiotensin system, sympathetic nervous activity, endothelin-1, sex hormones, aldosterone, and the immune system. Thus, gender-related antihypertensive treatment individualization may be a valuable tool in improving female patients’ prognosis.

Beneficial effects of oral supplementation with ferulic acid, a plant phenolic compound, on the human skin barrier in healthy men

Ferulic acid (FA) is a phytochemical compound with various physiologic functions. To clarify the effect of FA intake on skin barrier function (SBF), we conducted a placebo-controlled double-blind pilot trial. Sixteen healthy subjects were divided into 2 groups (n = 8) and ingested capsules containing either FA (200 mg) or placebo daily for 2 weeks. Two measures of SBF, transepidermal water loss and stratum corneum hydration, were assessed before and 2 weeks after the start of the study. Autonomic nervous activity, which is suggested to be related to SBF, was also measured. Compared with the values obtained before the start of the study, FA intake significantly reduced transepidermal water loss (from 6.1 ± 1.1 to 4.8 ± 1.0 g/m2/h, p = 0.005) and increased stratum corneum hydration (from 30.1 ± 7.6 to 32.3 ± 8.1 a.u., p = 0.027) after 2 weeks. In addition, the amount change in sympathetic nervous activity was significantly reduced after ingesting the FA capsules compared with the placebo capsules (−0.7 ± 1.6 vs. 1.1 ± 1.4, p = 0.035). These findings suggest that FA supplementation decreases sympathetic nervous activity and strengthens SBF in healthy men.

463 The Effect of Intervention of Medical Staff on the Adherence of CPAP and Heart Rate in Patients with Obstructive Sleep Apnea

Introduction Recent studies have indicated that obstructive sleep apnea syndrome (OSAS) is associated with hypertension. OSA is a common cause of sympathetic nervous activity. Increase of sympathetic nervous activity causes hypertension. Continuous positive airway pressure (CPAP) is the most useful treatment for OSAS. Good CPAP adherence treatment improve the risk of hypertension. This study examined the effect of intervention of medical staff on the adherence of CPAP, heart rate and sleep stages in patients with OSA. Methods All patients diagnosed with OSA and undergoing subsequent CPAP were clinically followed for 12 months to examine CPAP adherence, as well as longitudinal changes in blood pressure, average heartrate of 24 hours and sleep stages. They were divided into 2 groups, Group A: patients who had individual consulted in person by sleep physician and technicians before start using CPAP and Group B: patents who did not have individual consulted. Patients in both groups were consulted by sleep physician and technicians after start CPAP with utilizing tele-monitoring. If the adherence were poor, the patients were recommended to stop CPAP. We provided 3D accelerometer and an optical pulse photoplethysmography to all the patients and analyzed the data of heart rate and sleep stages. Results A total of 30 OSA patients underwent CPAP, were enrolled in the study and assessed for changes in mean heart rate and body weight during the study period. We found a significant reduction in mean heart rate in both group A and B compared with baseline (p&lt;-0.05). The patients aged under 50 years old and whose AHI&lt;20 times/hour have higher ratio of dropout CPAP therapy. There was no significant difference between Group A and Group B on the persistency rate of CPAP therapy. Also, no significant association was found between group A and B on the adherence of CPAP. Conclusion We showed the importance of the effect of intervention of medical staff on the adherence of CPAP and heart rate in patients with OSA the consultation after starting CPAP for a while with utilizing tele-monitoring data would be more effective compared with that in person before start using CPAP. Support (if any):