Concentrations Of Angiotensin Research Articles

Effects of intrarenal angiotensin 1-7 infusion on renal haemodynamic and excretory function in anaesthetised two-kidney one-clip and deoxycorticosterone acetate-salt hypertensive rats.

What is the central question of this study? Are renal functional responses to intrarenal angiotensin 1-7 (Ang (1-7)) infusion dependent on the level of the endogenous renin-angiotensin system (RAS) in the two-kidney one-clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt animal models of hypertension? What is the main finding and its importance? The renal actions of Ang (1-7) are dependent on the relative endogenous levels of each arm of the classical angiotensin II-angiotensin II type 1 receptor (AT1 R) axis and those of the Ang (1-7)-Mas receptor axis. These findings support the hypothesis that a balance exists between the intrarenal classical and novel arms of the RAS, and in particular the relative abundance of AT1 R to Mas receptor, which may to a large extent determine the renal excretory response to Ang (1-7) infusion. This study investigated the action of angiotensin 1-7 (Ang (1-7)) on renal haemodynamic and excretory function in the two-kidney one-clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt rat models of hypertension, in which the endogenous renin-angiotensin system (RAS) activity was likely to be raised or lowered, respectively. Rats were anaesthetised and prepared for the measurement of mean arterial pressure and kidney function during renal interstitial infusion of Ang (1-7) or saline. Kidney tissue concentrations of angiotensin II (Ang II) and Ang (1-7) were determined. Intrarenal infusion of Ang (1-7) into the clipped kidney of 2K1C rats increased urine flow (UV), absolute (UNa V) and fractional sodium (FENa ) excretions by 110%, 214% and 147%, respectively. Renal Ang II concentrations of the clipped kidney were increased with no major changes in Ang (1-7) concentration. By contrast, Ang (1-7) infusion decreased UV, UNa V, and FENa by 27%, 24% and 21%, respectively in the non-clipped kidney in which tissue Ang (1-7) concentrations were increased, but renal Ang II concentrations were unchanged compared to sham animals. Ang (1-7) infusion in DOCA-salt rats had minimal effects on glomerular filtration rate but significantly decreased UV, UNa V and FENa by ∼30%. Renal Ang (1-7) concentrations were higher and Ang II concentrations were lower in DOCA-salt rats compared to sham rats. These findings demonstrate that the intrarenal infusion of exogenous Ang (1-7) elicits different renal excretory responses the magnitude of which is dependent on the balance between the endogenous renal Ang II-AT1 receptor axis and Ang (1-7)-Mas receptor axis.

Concentrations of Soluble Angiotensin Converting Enzyme 2 (sACE2) in Children and Adults with and without COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19) pandemic, leads to illness and death. Various risk factors for a severe course, such as higher age, male gender and pre-existing illnesses are known. However, pathophysiological risk factors are largely unclear. Notably, the mild course of disease in children is conspicuous. Angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2 and is a key enzyme in infection. Differences in the distribution of ACE2 can provide insights into different courses of COVID-19. Our aim was to elucidate the role of ACE2 as a pathophysiological risk factor by measuring soluble ACE2 (sACE2) via ELISA in blood samples (lithium-heparin-plasma or serum) of 367 individuals including children and adults with and without COVID-19. sACE2-levels were compared between the groups according to age and sex. In adults and children with COVID-19, sACE2-concentrations are significantly higher compared to healthy individuals. sACE2-levels increase with age and are lower in children compared to adults with COVID-19. Sex doesn't significantly influence sACE2-concentration. It remains unclear whether sACE2 concentrations increase because of the infection and what factors could influence this response. In conclusion, the increase of sACE2-concentration with age could indicate that ACE2 concentrations mirror increased COVID-19 severity.

Platelet TGF-β1 inhibits the migration and proliferation of smooth muscle cells in aneurysms

BackgroundThe study explored the role of platelet TGF-β1 from the perspective of inhibiting the excessive proliferation, migration and invasion of murine aortic vascular smooth muscle cells (MASMCs). MethodThe platelets were first extracted from C57BL/6 mice, and the TGF-β1 protein was obtained after the purification of protein. In vitro, the concentrations of angiotensin Ⅱ (Ang Ⅱ) and TGF-β1 for intervention were screened by testing the viability of MASMCs, followed by the analysis concerning the effects of platelets, Ang Ⅱ and TGF-β1 on the proliferation, migration, invasion, and the expressions of pathway-related proteins in MASMCs. In vivo, an Ang Ⅱ-induced mouse model was established. TGF-β1 was injected into the tail of mice as a therapeutic agent, and its action mechanism was further verified by the treatment of inhibitor SB505124. The results of the cell experiment were validated by evaluating the maximum diameter of abdominal aorta, the proportion of total weight, the changes of both pathology and the expressions of pathway-related proteins in the mice. Result0.5 ng/mL Ang Ⅱ and 15 ng/mL TGF-β1 were chosen for treatment. The following results of cell functional experiments and Western blot assay demonstrated that Ang Ⅱ promoted the proliferation, migration and invasion of MASMCs via regulating related pathways, the effects of which were evidently reversed by TGF-β1 and platelets. Consistent results were also observed in the animal experiments, where TGF-β1 effectively alleviated Ang Ⅱ-induced abdominal aortic injury in mice. ConclusionTGF-β1 in platelets inhibits Ang Ⅱ-induced proliferation, migration and invasion of MASMCs.

Potential autonomic nervous system dysfunction in COVID-19 patients detected by heart rate variability is a sign of SARS-CoV-2 neurotropic features.

Increasing evidence strongly support that the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to the development of COVID-19-associated central nervous system (CNS) manifestations. The presence of SARS-CoV-2 viral protein in the brainstem, which includes cardiovascular control centers, has been documented previously. Given the changes in autonomic nervous system function evaluated by heart rate variability (HRV) metrics, which are observed even prior to clinical signs, the potential effect of SARS-CoV-2 on the autonomic nervous system (ANS) center is likely. The integral parts of the brain renin-angiotensin system, as ACE2 enzyme, are highly expressed in the brainstem, which may also be involved in baroreflex sensitivity, playing an important role in HRV. SARS-CoV-2 may bind to ACE2 in order to enter the host brainstem cell and change baroreflex sensitivity due to the altered ratio of the concentration of angiotensin II (Ag II) to angiotensin (1-7). In this article, we discussed the information on the possibility that the SARS-CoV-2 viral particle by disrupting the homeostasis of the brain renin-angiotensin system even without brainstem neuropathological changes, may affect the function of the ANS center in the brainstem. SARS-CoV-2 could influence ANS function before affecting the immune system. It is possible that the altered HRV parameters imply the potential neurotropic characteristics of SARS-CoV-2. Therefore, this potential feature should be taken into account in diagnostic and therapeutic approaches for COVID-19 patients.

UPREGULATION OF NADH/NADPH OXIDASE 4 BY ANGIOTENSIN II INDUCES PODOCYTE APOPTOSIS

Objective: Angiotensin II induces glomerular and podocyte injury via systemic and local vasoconstrictive or non-hemodynamic effects including oxidative stress. The release of free radicals from podocytes may participate in the development of glomerular injury and proteinuria. We studied the pathophysiologic roles of oxidative stress in angiotensin II-induced podocyte apoptosis. Design and method: Mouse podocytes were incubated in media containing various concentrations of angiotensin II and at different incubation times and transfected by Nox4 or AT1R siRNAs or negative control scrambled siRNA for 24 h. The changes of podocyte oxidative stress and apoptosis were observed by confocal imaging, western blotting, realtime PCR, FACS and TUNEL assay according to the presence of angiotensin II. Results: Angiotensin II increased the generation of mitochondrial superoxide anions and reactive oxygen species levels but suppressed superoxide dismutase activity that was reversed by probucol, an antioxidant. Angiotensin II also increased NADH/NADPH oxidase 4 protein and expression in a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of NADH/NADPH oxidase 4 by siRNA reduced the oxidative stress induced by angiotensin II. Furthermore, angiotensin II promoted podocyte apoptosis that was reduced significantly by probucol and NADH/NADPH oxidase 4 siRNA, and also recovered by angiotensin II type 1 receptor siRNA. In sum, angiotensin II induced podocyte oxidative stress and apoptosis through NADH/NADPH oxidase 4 and angiotensin II type 1 receptor. Conclusions: These findings suggest that angiotensin II promoted podocyte mitochondrial oxidative stress resulting in apoptosis via the upregulation of NADH/NADPH oxidase 4 and angiotensin II type 1 receptor and, which could be prevented by NADH/NADPH oxidase 4 inhibition and/or antagonizing angiotensin II type 1 receptor as well as antioxidants.

MO003: Upregulation of NADH/NADPH Oxidase 4 by Angiotensin II Induces Podocyte Apoptosis

Abstract BACKGROUND AND AIMS Oxidative stress induced by non-hemodynamic effects of angiotensin II in podocytes participates in the development of glomerular injury and proteinuria. We studied the pathophysiologic roles of oxidative stress in angiotensin II-induced podocyte apoptosis. METHOD Mouse podocytes were incubated in media containing various concentrations of angiotensin II at different incubation times and transfected by Nox4 or AT1R siRNAs or negative control scrambled siRNA for 24 h. The changes of podocyte oxidative stress and apoptosis were observed by confocal imaging, western blotting, real-time PCR, FACS and TUNEL assays according to the presence of angiotensin II. RESULTS Angiotensin II increased the generation of mitochondrial superoxide anions and reactive oxygen species levels but suppressed superoxide dismutase activity that was reversed by probucol, an antioxidant. Angiotensin II also increased NADH/NADPH oxidase 4 protein and expression in a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of NADH/NADPH oxidase 4 by siRNA reduced the oxidative stress induced by angiotensin II. Furthermore, angiotensin II promoted podocyte apoptosis that was reduced significantly by probucol and NADH/NADPH oxidase 4 siRNA, and also recovered by angiotensin II type 1 receptor siRNA. In sum, angiotensin II induced podocyte oxidative stress and apoptosis through NADH/NADPH oxidase 4 and angiotensin II type 1 receptor. CONCLUSION These findings suggest that angiotensin II promotes podocyte mitochondrial oxidative stress, resulting in apoptosis via the upregulation of NADH/NADPH oxidase 4 and angiotensin II type 1 receptor, which could be prevented by NADH/NADPH oxidase 4 inhibition and/or antagonizing angiotensin II type 1 receptor as well as antioxidants.

Constrictor Responses of Cerebral Resistance Arterioles Preserved in Male and Female Rats Exposed to Prenatal Alcohol

Fetal alcohol spectrum disorder (FASD) is the result of exposure to alcohol in utero. This disorder causes lifelong intellectual and behavioral disabilities, as well as cardio and cerebrovascular dysfunction. However, the mechanisms by which these abnormalities arise are poorly understood, and no treatment exists. Past studies have shown that dilation of cerebral arterioles to nitric oxide synthase (NOS)‐dependent agonists is impaired in rats exposed to prenatal alcohol, yet no studies have examined the influence of prenatal alcohol on constrictor responses of cerebral arterioles. We hypothesize that in uteroalcohol exposure may impair the activity of the vascular smooth muscle, which could lead to an alteration in the ability of the cerebral arterioles to constrict in response to endogenous vasoconstrictor agents. Therefore, the goal of this study was to determine whether responses of cerebral arterioles to vasoconstrictors are altered in rats exposed to alcohol in utero. We fed Sprague‐Dawley dams a liquid diet with or without alcohol (3% ethanol) for the duration of their pregnancy (21‐23 days). We then examined the reactivity of the cerebral arterioles of the pups to arginine vasopressin (AVP; 0.1 and 1 nM), thromboxane (U‐46619; 10 and 100 nM), and angiotensin II (1 and 10 µM) in four groups: control male, control female, prenatal alcohol male, and prenatal alcohol female, at two different age ranges: 4‐6 weeks of age and 14‐16 weeks of age. We found that constrictor responses of cerebral arterioles to AVP and the thromboxane analog (U‐46619) were similar in control rats and rats exposed to prenatal alcohol at both age groups for both sexes. In addition, adolescent male and female rats showed no difference to angiotensin II following prenatal exposure to alcohol. However, alcohol‐exposed females exhibited an unexpected dilation to the high concentration of angiotensin II in adulthood, which was absent in males. We suggest that the findings from these studies may have implications regarding the susceptibility of the brain to cerebral ischemic damage. We speculate that impaired vasodilation, with preserved vasoconstriction, can lead to a scenario favoring a decrease in cerebral blood flow during times of increased metabolic demand. This is the first published study to examine the influence of in uteroexposure to alcohol on constrictor responses of cerebral arterioles. Further understanding of how cerebrovascular blood flow may be altered in rats with FASD can ultimately lead to an understanding of how the resulting ischemic damage may relate to intellectual and behavioral abnormalities.

Angiotensin II and atrial natriuretic peptide — unity and struggle of opposites in the model of renovascular hypertension “2 kidneys, 1 clamp”: A meta-analysis

Background. Today, the Goldblatt model of hypertension “2 kidneys, 1 clamp” has been investigated in a large number of experimental studies. The activation of the renin-angiotensin system (RAS) underlies the development of this type of hypertension. The main buffer of the RAS is the atrial natriuretic peptide (ANP), its level is significantly increased in response to blood pressure (BP) elevation and high concentration of angiotensin II and Na+. ANP has a pronounced hypotensive effect. Clinical and experimental studies show that unilateral renovascular hypertension (URH) does not always develop even in significant stenosis of the renal artery. The purpose of this work is to investigate the activity of the RAS and the ANP, shifts in the water-electrolyte balance and renal sympathetic nervous activity via meta-analysis, to evaluate hypertensive and hypotensive mechanisms in the model of renovascular hypertension “2 kidneys, 1 clamp”. Design and methods. The meta-analysis was carried out by statistical program Review Manager 5.3 (Cochrane Library). In a meta-analysis, we used 76 publications of experimental studies of the model of renovascular hypertension in rats. Results and conclusions. The meta-analysis showed that the maintenance of URH is ensured by the high activity of the RAS and the sympathetic nervous system, as well as hypokalemia and cardiovascular remodeling. However. there is no convincing evidence of the effect of sodium-volume-dependent mechanisms on BP elevation in this model of hypertension.

Gypenoside IX Ameliorates Hypertension Induced by Obesity via Inactivation of the Mitogen-Activated Protein Kinase Pathway

Gynostemma pentaphyllum (Thunb.) Makino is a Chinese herb known to alleviate hyperlipidemia and obesity. In the present study, the effect and the mechanism of the effect of gypenoside IX, a bioactive constituent of G. pentaphyllum on the obesity-related hypertension in rats has been explored. The rats were fed a high fat diet to induce obesity leading to hypertension. Treatment of these hypertensive rats with gypenoside IX resulted in decreased systolic and diastolic blood pressure, body weight, and alleviation of pathological manifestations in myocardium and aorta. Furthermore, gypenoside IX antagonized the high fat diet-induced relative increase in the expressions of angiotensin-converting enzyme, angiotensin II receptor type 1 and 2 proteins, and the B-type natriuretic peptide and atrial natriuretic peptide messenger RNAs. However, the concentrations of angiotensin II, adrenaline, and norepinephrine increased, whereas that of cyclic guanosine monophosphate decreased. The levels of malondialdehyde increased and that of reduced glutathione, superoxide dismutase, and catalase decreased in high fat diet rats that were reversed by the gypenoside IX treatment. There was a significant increase in the relative protein levels for phospho-extracellular signal-regulated kinase/extracellular signal-regulated kinase, phospho-c-Jun NH2-terminal kinase/c-Jun NH2-terminal kinase, and p-p38/p-38 that was ameliorated by gypenoside IX. In conclusion, gypenoside IX inhibits the renin–angiotensin system activation and oxidative stress through the inactivation of the mitogen-activated protein kinase pathway in obesity-mediated hypertension in rats.

Does the Serum Concentration of Angiotensin II Type 1 Receptor Have an Effect on the Severity of COVID-19? A Prospective Preliminary Observational Study among Healthcare Professionals.

SARS-CoV-2 is a virus that causes severe respiratory distress syndrome. The pathophysiology of COVID-19 is related to the renin–angiotensin system (RAS). SARS-CoV-2, a vector of COVID-19, uses angiotensin-converting enzyme 2 (ACE-2), which is highly expressed in human lung tissue, nasal cavity, and oral mucosa, to gain access into human cells. After entering the cell, SARS-CoV-2 inhibits ACE-2, thus favouring the ACE/Ang II/angiotensin II type 1 receptor (AT1R) axis, which plays a role in the development of acute lung injury (ALI). This study aimed to analyse the influence of angiotensin 1 receptor (AT1R) levels in the serum on the course of the severity of symptoms in healthcare professionals who had a SARS-CoV-2 infection. This prospective observational study was conducted on a group of 82 participants. The study group included physicians and nurses who had a COVID-19 infection confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2. The control group consisted of healthy medical professionals who had not had a SARS-CoV-2 infection or who had no symptoms of COVID-19 and who tested negative for SARS-CoV-2 on the day of examination. We analysed the correlation between AT1R concentration and the severity of COVID-19, as well as with sex, age, blood group, and comorbidities. There were no statistically significant differences in the mean values of AT1R concentration in the recovered individuals and the non-COVID-19 subjects (3.29 vs. 3.76 ng/mL; p = 0.32). The ROC curve for the AT1R assay showed an optimal cut-off point of 1.33 (AUC = 0.44; 95% CI = 0.32–0.57; p = 0.37). There was also no correlation between AT1R concentration and the severity of symptoms associated with COVID-19. Blood type analysis showed statistically significantly lower levels of AT1R in COVID-19-recovered participants with blood group A than in those with blood group O. In conclusion, AT1R concentration does not affect the severity of symptoms associated with COVID-19 among healthcare professionals.

Circulating renin-angiotensin-aldosterone system activity in cats with systemic hypertension or cardiomyopathy.

BackgroundActivity of the circulating renin‐angiotensin‐aldosterone system (RAAS) has not been comprehensively characterized in cats with systemic hypertension (SH) or cardiomyopathy (CM), and the effects of furosemide or amlodipine treatment on the RAAS have not been fully evaluated in cats.Hypothesis/ObjectivesTo document RAAS activity in cats with SH or CM compared to healthy cats and determine how RAAS profiles change with furosemide or amlodipine treatment.AnimalsSixty‐six client‐owned cats: 15 with SH (7 amlodipine‐treated, 8 untreated), 17 with advanced CM (7 furosemide‐treated, 10 not furosemide‐treated), and 34 healthy cats.MethodsEquilibrium concentrations of RAAS peptides and aldosterone were quantified in serum samples by liquid chromatography‐mass spectrometry. Variables were compared between groups using Kruskal‐Wallis analysis with post hoc Holms‐corrected Dunn's testing.ResultsCompared with healthy cats, cats with CM had higher concentrations of angiotensin I, aldosterone, and plasma renin activity (all P < .01), and these differences remained significant (P < .03) after considering subgroups of untreated or furosemide‐treated cats. Compared with healthy cats, untreated cats with SH showed no differences in RAAS biomarkers, whereas amlodipine‐treated cats had higher concentrations of angiotensins I, II, III, IV, and 1‐7, aldosterone, and plasma renin activity (all P < .03). Multivariable analysis determined that furosemide and amlodipine treatments were independent predictors of increased RAAS biomarker concentrations.Conclusions and Clinical ImportanceCats with CM had increased RAAS activity, whereas cats with untreated SH did not. Furosemide and amlodipine both led to nonspecific activation of both classical and alternative RAAS pathways in cats.

Assessment of the state and relationship of vasopressor and renin-angiotensin systems in patients with localized kidney cancer on the background of arterial hypertension

Background. Vasopressin, in cooperative interaction with angiotensin II, participates in cardiovascular regulation and it increases in arterial hypertension. In addition, vasopressin is involved in tumorigenesis through angiogenesis by stimulating protein synthesis in endothelial cells, induction of endothelin-1, influencing cell proliferation, and stimulating growth factors through VIA receptors in the kidneys. To assess the content of vasopressin, a measurement of copeptin, its precursor, produced in an equimolar ratio, is used.Objective: to determine the content of serum copeptin and to reveal correlations with the indices of the renin-angiotensin system in the tumor and blood serum in patients with localized kidney cancer (КС) with arterial hypertension (AH).Materials and methods. The inclusion criteria for the study were initially diagnosed localized KC T1N0M0 without special treatment, age less than 75 years, essential AH of I—II degree without treatment, controlled by angiotensin-converting enzyme inhibitors (ACEi). All patients were divided into groups: patients with KC (n = 42); KC + AH without treatment (n = 31); KC + AH + ACEi (n = 32). Serum levels of copeptin and angiotensin I, II, 1-7 and angiotensin-converting enzyme, angiotensin-converting enzyme 2 were determined by ELISA. Also, the level of components of the renin-angiotensin system was assessed in tumor tissue samples obtained by robotic-assisted kidney resection.Results and conclusion. In patients of the KC + AH group, the median of the indicator is statistically significantly higher than in the group of healthy donors (2.4 times at p &lt;0.05). In the group KC + AH + ACEi, a decrease in the content of the studied indicator was found in comparison with the norm by 1.2 times (at p &lt;0.05). It was found that the content of copeptin in the tumor less than 4 cm in comparison with the size of 4-7 cm is significantly lower (KC p = 0.045, KC + AH p = 0.067 and KC + AH + ACEi p = 0.036). Correlation analysis showed direct significant links between high density between the levels of copeptin and angiotensin II in the tumor and blood, and moderate tightness with tumor and serum levels of angiotensin (1-7). Multiple regression analysis revealed that the most significant factors that have a positive effect on the concentration of serum copeptin are the content of angiotensin II in the tumor and blood serum, the tumor concentration of angiotensin (1-7) and angiotensin-converting enzyme 2, as well as the level of systolic blood pressure (p &lt;0.05).

Characterization of the intrarenal renin‐angiotensin system in cats with naturally occurring chronic kidney disease

BackgroundThe role of the renin‐angiotensin‐aldosterone system in cats with chronic kidney disease (CKD) is incompletely understood.ObjectiveTo characterize components of the intrarenal renin‐angiotensin system (RAS) in cats with CKD.AnimalsEleven cats with naturally occurring CKD (CKD group) and 8 healthy control cats.MethodsRenal tissue samples were evaluated by reverse‐transcription polymerase chain reaction for renin, angiotensinogen, angiotensin‐converting enzyme (ACE), and angiotensin II type 1 receptor transcript levels, and by liquid chromatography‐mass spectrometry for quantification of angiotensin I, II, III, and IV concentrations. Linear mixed models were used to compare gene transcript levels and concentrations of angiotensin peptides between groups.ResultsCats of the CKD group were significantly older (P < .001) and more likely to be neutered (P = .007) than healthy control cats. Kidneys from cats with CKD had significantly higher transcript levels of angiotensinogen (P < .001) and lower transcript levels of ACE (P < .001) than those from control cats. Renal angiotensin I concentrations were increased in CKD compared with control kidneys (P = .001). No other significant differences in renal transcript levels or angiotensin peptide concentrations were noted between groups.Conclusion and Clinical ImportanceThe intrarenal RAS might be activated in cats with CKD. Small sample size and differences in age, neuter status, and dietary sodium intake between groups might have limited the ability to identify a significant difference in concentration of renal angiotensin II.

Serum concentrations of osteoprotegerin, brain-derived nerve factor, angiotensin II, and endothelin-1 in aging dogs.

Gerontology is a major research topic in veterinary medicine; however, there are few reports on changes in biomarker levels in aged dogs. The purpose of this preliminary study was to evaluate the differences in serum biomarker levels between young (less than 36 months) and old (over 108 months) companion dogs. We measured the serum concentrations of brain-derived neurotrophic factor (BDNF), osteoprotegerin (OPG), angiotensin II (ANGII), and endothelin-1 (ET-1) in both groups (young: n = 16, 19.8 ± 9.3 months old; old: n = 16, 155.8 ± 22.8 months old). Although the concentrations of BDNF did not differ between the two groups, the OPG, ANGII, and ET-1 levels were significantly higher in the old companion dogs than in the young dogs (p < 0.05). OPG, ANGII, and ET-1 concentrations may increase in dogs during aging.

Constrictor responses of cerebral resistance arterioles in male and female rats exposed to prenatal alcohol.

While it is known that dilation of cerebral arterioles to NOS‐dependent agonists is impaired in rats exposed to prenatal alcohol, no studies have examined the influence of prenatal alcohol on constrictor response of cerebral arterioles. Our goal was to determine whether constrictor responses of cerebral resistance arterioles are altered by prenatal exposure to alcohol and if any changes differed as a function of age or sex. We fed Sprague‐Dawley rat dams a liquid diet with or without alcohol (3% ethanol) for the duration of their pregnancy. We then examined reactivity of cerebral arterioles to thromboxane (U‐46619; 0.01 and 0.1 µM), arginine vasopressin (0.1 and 1 nM), and angiotensin II (1 and 10 µM) in four groups of offspring: control male and female, and prenatal alcohol male and female at two different ages (adolescent: 4–6 weeks old and adult: 14–16 weeks old). Constriction of cerebral arterioles to U‐46619 and AVP were similar in male and female rats regardless of exposure to prenatal alcohol and age. Similarly, adolescent male and female rats showed no difference to angiotensin II following prenatal exposure to alcohol. However, alcohol‐exposed females exhibited an unexpected dilation to the high concentration of angiotensin II in adulthood, which was absent in males. We suggest that the findings from these studies may have implications regarding the susceptibility of the brain to cerebral ischemic damage. We speculate that impaired vasodilation, coupled with preserved vasoconstriction, can lead to a scenario favoring a decrease in cerebral blood flow during times of increased metabolic demand.

Renal denervation based on experimental rationale.

Excessive activation of the sympathetic nervous system is one of the pathophysiological hallmarks of hypertension and heart failure. Within the central nervous system, the paraventricular nucleus (PVN) of the hypothalamus and the rostral ventrolateral medulla in the brain stem play critical roles in the regulation of sympathetic outflow to peripheral organs. Information from the peripheral circulation, including serum concentrations of sodium and angiotensin II, is conveyed to the PVN via adjacent structures with a weak blood-brain barrier. In addition, signals from baroreceptors, chemoreceptors and cardiopulmonary receptors as well as afferent input via the renal nerves are all integrated at the level of the PVN. The brain renin-angiotensin system and the balance between nitric oxide and reactive oxygen species in these brain areas also determine the final sympathetic outflow. Additionally, brain inflammatory responses have been shown to modulate these processes. Renal denervation interrupts both the afferent inputs from the kidney to the PVN and the efferent outputs from the PVN to the kidney, resulting in the suppression of sympathetic outflow and eliciting beneficial effects on both hypertension and heart failure.

Potassium Alginate Oligosaccharides Alter Gut Microbiota, and Have Potential to Prevent the Development of Hypertension and Heart Failure in Spontaneously Hypertensive Rats.

Food-derived oligosaccharides show promising therapeutic potential in lowering blood pressure (BP), but the mechanism is poorly understood. Recently, the potential role of gut microbiota (GM) in hypertension has been investigated, but the specific GM signature that may participate in hypertension remains unclear. To test the potassium alginate oligosaccharides (PAO) mechanism in lowering BP and specific microbial signature changes in altering GM, we administered various dosages of PAO in 40 spontaneously hypertensive rats for a duration of six weeks. We analyzed BP, sequenced the 16S ribosomal DNA gene in the cecum content, and gathered RNA-seq data in cardiac tissues. We showed that the oral administration of PAO could significantly decrease systolic BP and mean arterial pressure. Transcriptome analyses demonstrated that the protective effects of developing heart failure were accompanied by down-regulating of the Natriuretic Peptide A gene expression and by decreasing the concentrations of angiotensin II and atrial natriuretic peptide in plasma. In comparison to the Vehicle control, PAO could increase the microbial diversity by altering the composition of GM. PAO could also decrease the ratio of Firmicutes to Bacteroidetes by decreasing the abundance of Prevotella and Phascolarctobacterium bacteria. The favorable effect of PAO may be added to the positive influence of the abundance of major metabolites produced by Gram-negative bacteria in GM. We suggest that PAO caused changes in GM, and thus, they played an important role in preventing the development of cardiovascular disease.

EIF3D promotes the progression of preeclampsia by inhibiting of MAPK/ERK1/2 pathway

Preeclampsia (PE) has been recognized as one of the main reasons for neonatal and maternal mortality and morbidity. This study intended to identify certain genes that correlated with the pathogenesis of PE, and disclose the underlying mechanisms. The GSE14776 and GSE65271 datasets were obtained from the Gene Expression Omnibus database. Venn diagram analysis was performed to identify the differently expressed genes. The potential pathways were analyzed by Gene set enrichment analysis software. The expression of eukaryotic translation initiation factor 3 subunit D (EIF3D) in tissues and cells was respectively tested by immunohistochemistry and the quantitative real-time PCR. Cell transfection was utilized to alter the expression of EIF3D. Cell proliferation, invasion and migration were respectively tested by MTT, EdU, transwell and wound healing assays. Tube formation assay was utilized to determine the tube formation capacity of HTR-8/SVneo cells. ELISA was employed for determination of the concentration of Angiotensin (ANG)-1. Moreover, the expression of EIF3D, proliferation-, metastasis-, tube formation- and MAPK/ERK1/2 pathway-related proteins were measured utilizing western blot. EIF3D was selected in this study. EIF3D was upregulated in placentas tissues collected from patients with PE. EIF3D upregulation observably repressed the proliferation, invasion, migration, wound healing and tube formation of HTR-8/SVneo cells, and the expression of their associated proteins. Besides, the concentration of ANG-1, and the ratios of phosphorylated-ERK1/2 and phosphorylated-MEK1/MEK1 were also markedly lowered by EIF3D upregulation. Whereas, EIF3D knockdown exerted the opposite effects, and these effects were distinctly counteracted by ERK1/2 inhibitor SC-221593 treatment. In conclusion, these observations manifested that EIF3D upregulation might have repressed the progression of PE through modulation of MAPK/ERK1/2 pathway.

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

Salt-contaminated water inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in broilers.

NaCl is the main component of freshwater salinization. High NaCl concentration in drinking water can cause pulmonary hypertension syndrome (PHS) and kidney damage in broilers. To explore the effect of NaCl in drinking water on broilers' kidneys, this study divided 80 chickens into four groups. With the control group fed with pure water, broiler chickens were fed with fresh water (FW, NaCl 1 g/L), low salt-contaminated water (L-SCW, NaCl 2.5 g/L), and high salt-contaminated water (H-SCW, NaCl 5 g/L). The results show that ascites heart index (AHI) and hematocrit (HCT) of broilers increase in L-SCW and H-SCW, the serum blood urea nitrogen and creatinine of broilers increase significantly, the kidney index increases, the kidney sections show vacuolar degeneration and fibrotic degeneration, and the TUNEL results show that the kidneys possess obvious apoptosis. In addition, the detection of RAAS-related genes (AGT gene in the liver, REN in the kidney, ACE in the lung) demonstrates that after using salt-contaminated water, the transcription levels of AGT, REN, and ACE rise significantly, and the concentration of angiotensin II (Ang II) also increases significantly. In order to verify the effect of Ang II on broiler kidneys, this research used exogenous Ang II to treat chicken embryonic kidney (CEK) cells. The results show that the cell activity of CEK decreased with the increase of the concentration of exogenous Ang II. Meanwhile, the flow cytometry assay shows that Ang II could promote the apoptosis of CEK cells. These results indicate that the salt-contaminated water can aggravate PHS and cause kidney damage. The mechanism may be related to the increase of Ang II.