Salt-induced Hypertensive Rats Research Articles

The effect of ethanolic Acalypha Wilkesiana extract on blood sugar, sodium, potassium levels in alloxan-induced diabetic and salt-induced hypertensive Wistar rats

Diabetes Mellitus and hypertension often occur simultaneously. Hypertension affects approximately 70% of patients with diabetes, and the risk of cardiovascular disease in diabetic patients is three times higher than that in healthy individuals. The study was aimed at investigating the problem of diabetes and hypertension, and a possible remedy for it. Twenty-five (25) male wistar rats were assigned into five (5) groups of five (5) rats each. Group A served as negative control, and received water and feed only. Group B served as the positive control, and received alloxan160 mg/kg BW+ salt-loaded diet. Group C-E received alloxan 160 mg/kg BW+ salt-loaded diet + 100 mg/kg BW, 200 mg/kg BW, and 300 mg/kg BW of ethanolic acalypha wilkesiana (EAW) respectively. All administrations were given orally twice daily for 21 days. At the end of the treatment, blood samples were collected to estimate blood glucose, insulin, sodium, and potassium levels. Results are presented as mean±SEM, and were analysed using One-way ANOVA, statistical significance was considered at (P≤0.05). The results showed decrease in blood glucose levels and increase in insulin levels in groups C, D, and E compared to group B. There was also a decrease in sodium ion levels, and a concomitant increase in potassium ion levels in all wistar rat treatment groups when compared to group B. In summary, the results showed improved blood sugar, insulin, sodium, and potassium ion levels following EAW administration. It is therefore concluded that EAW administration was effective in improving diabetic and hypertensive complications in wistar rats.

Retracted: Antihypertensive Activity in High Salt-Induced Hypertensive Rats and LC-MS/MS-Based Phytochemical Profiling of Melia azedarach L. (Meliaceae) Leaves.

[This retracts the article DOI: 10.1155/2022/2791874.].

Effectiveness of avocado leaf extract (Persea americana Mill.) as antihypertensive

Background Avocado leaves (Persea americana Mill.) have been traditionally used as antihypertensive. Various studies have tested the benefits of the Persea americana Mill. in treating hypertension but still using extracts not yet using nanoparticles. Therefore, this study aims to study the effectiveness of avocado leaf extract, including the nanoparticles, on salt-induced hypertensive Wistar rats in inhibiting the ACE enzyme, which causes decreasing systolic blood pressure (SBP) and diastolic blood pressure (DBP) as well as increasing urine volume. Methods This study used an experimental in vivo study design involving 24 white male Wistar rats (Rattus norvegicus), aged 2–3 months, weighing 130–250 g, and of a healthy condition with active movement. The samples were randomly divided into six treatment groups and post-test only research design with control group design. Results The result of the study showed that the extract contained a quercetin of 1129.597 ppm and 10 mineral compounds, including potassium, with the highest content. The analysis of antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl method showed that the antioxidant activity at IC50 was 44.734 ppm. The P. americana leaf extract nanoparticles had the most significant result in reducing blood pressure in Wistar rats induced by 16% NaCl for 14 days SBP to normal was by 68.75 mmHg (175.00±21.57 mmHg to 106.25±9.21 mmHg) and 55.25 mmHg (128.42±25.75 mmHg to 73.17±15.75 mmHg), respectively. Also, avocado leaf extract caused the decrease of SBP from 164.92±7.16 mmHg to 116.83±6.36 mmHg and DBP from 118.42±16.24 mmHg to 82.83±6.47 mmHg. The P. americana leaf extract nanoparticles resulted in the most urine volume at 13.5 ml, with the highest DAI value of 2.25. The ACE inhibitor test using the ELISA method showed that the P. americana leaf extract and the nanoparticle extract inhibition against the ACE enzyme were 60.0±12.1 % and 59.5±3%, respectively. The mean serum nitrate as a result of P. americana leaf extract (K4) and nanoparticles of P. americana leaf extract (K5) were 44.0±9.0 μmol/L and 41.1±11.5 μmol/L, respectively. The mean of serum nitrite was led by P. americana leaf extract (K4), and nanoparticles of P. americana leaf extract (K5) were 83.7±24.0 μmol/L and 81.0±23.2 μmol/L, sequentially. Conclusions The study showed that the leaf extract and nanoparticle extract of Persea americana Mill. was effective as an antihypertensive.

Curcumin Nanoemulsion: Unveiling Cardioprotective Effects via ACE Inhibition and Antioxidant Properties in Hypertensive Rats.

Background and Objectives: Curcumin, derived from Curcuma longa, is a well-known traditional medicinal compound recognized for its therapeutic attributes. Nevertheless, its efficacy is hampered by limited bioavailability, prompting researchers to explore the application of nanoemulsion as a potential alternative. Materials and Methods: This study delves into the antihypertensive effects of curcumin nanoemulsion (SNEC) by targeting the renin-angiotensin-aldosterone system (RAAS) and oxidative stress in deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats. To gauge the cardio-protective impact of SNEC in DOCA salt-induced hypertension, molecular docking was undertaken, uncovering curcumin's high affinity and adept binding capabilities to the active site of angiotensin-converting enzyme (ACE). Additionally, the investigation employed uninephrectomized rats to assess hemodynamic parameters via an AD instrument. Serum ACE, angiotensin II, blood urea nitrogen (BUN), and creatinine levels were quantified using ELISA kits, while antioxidant parameters were evaluated through chemical assays. Result: The outcomes of the molecular docking analysis revealed robust binding of curcumin to the ACE active site. Furthermore, oral administration of SNEC significantly mitigated systolic, diastolic, and mean arterial blood pressure in contrast to the DOCA-induced hypertensive group. SNEC administration also led to a reduction in left ventricular end-diastolic pressure (LVEDP) and an elevation in the maximum rate of left ventricular pressure rise (LV (dP/dt) max). Moreover, SNEC administration distinctly lowered serum levels of ACE and angiotensin II compared to the hypertensive DOCA group. Renal markers, including serum creatinine and BUN, displayed a shift toward normalized levels with SNEC treatment. Additionally, SNEC showcased potent antioxidant characteristics by elevating reduced glutathione, catalase, and superoxide dismutase levels, while decreasing the concentration of thiobarbituric acid reactive substances. Conclusions: Collectively, these findings underscore that curcumin nanoemulsion exerts noteworthy cardio-protective effects through ACE activity inhibition and remarkable antioxidant properties.

Upregulation of Piezo2 in the mesangial, renin, and perivascular mesenchymal cells of the kidney of Dahl salt-sensitive hypertensive rats and its reversal by esaxerenone.

The recent discovery of mechanosensitive ion channels has promoted mechanobiological research in the field of hypertension and nephrology. We previously reported Piezo2 expression in mouse mesangial and juxtaglomerular renin-producing cells, and its modulation by dehydration. This study aimed to investigate how Piezo2 expression is altered in hypertensive nephropathy. The effects of the nonsteroidal mineralocorticoid receptor blocker, esaxerenone, were also analyzed. Four-week-old Dahl salt-sensitive rats were randomly assigned to three groups: rats fed a 0.3% NaCl diet (DSN), rats fed a high 8% NaCl diet (DSH), and rats fed a high salt diet supplemented with esaxerenone (DSH + E). After six weeks, DSH rats developed hypertension, albuminuria, glomerular and vascular injuries, and perivascular fibrosis. Esaxerenone effectively decreased blood pressure and ameliorated renal damage. In DSN rats, Piezo2 was expressed in Pdgfrb-positive mesangial and Ren1-positive cells. Piezo2 expression in these cells was enhanced in DSH rats. Moreover, Piezo2-positive cells accumulated in the adventitial layer of intrarenal small arteries and arterioles in DSH rats. These cells were positive for Pdgfrb, Col1a1, and Col3a1, but negative for Acta2 (αSMA), indicating that they were perivascular mesenchymal cells different from myofibroblasts. Piezo2 upregulation was reversed by esaxerenone treatment. Furthermore, Piezo2 inhibition by siRNA in the cultured mesangial cells resulted in upregulation of Tgfb1 expression. Cyclic stretch also upregulated Tgfb1 in both transfections of control siRNA and Piezo2 siRNA. Our findings suggest that Piezo2 may have a contributory role in modulating the pathogenesis of hypertensive nephrosclerosis and have also highlighted the therapeutic effects of esaxerenone on salt-induced hypertensive nephropathy. Mechanochannel Piezo2 is known to be expressed in the mouse mesangial cells and juxtaglomerular renin-producing cells, and this was confirmed in normotensive Dahl-S rats. In salt-induced hypertensive Dahl-S rats, Piezo2 upregulation was observed in the mesangial cells, renin cells, and notably, perivascular mesenchymal cells, suggesting its involvement in kidney fibrosis.

Vasorelaxant and Antihypertensive Effects of Bergenin on Isolated Rat Aorta and High Salt-Induced Hypertensive Rats.

Bergenin is a phenolic glycoside that has been reported to be present in some medicinal plants which are traditionally used for their antihypertensive actions. So, bergenin was investigated for antihypertensive and vasorelaxant experiments in a rat model. Bergenin produced a significant fall in the mean arterial pressure (MAP) of rats. To explore the involvement of NO and muscarinic receptors, rats were pretreated with L-NAME and atropine in-vivo. The L-NAME did not change significantly the effect of bergenin on MAP excluding the involvement of NO. Unlike the L-NAME, atropine pretreatment reduced the effect of bergenin on MAP, indicating the role of muscarinic receptors. In in-vitro study, the bergenin produced endothelium-dependent (at lower concentrations) and independent (at higher concentrations) vasorelaxation, which was attenuated significantly in the presence of atropine and indomethacin but not with L-NAME. While a partial response was observed against K+-induced contractions. This was further confirmed when bergenin partly shifted the CaCl2-CRCs toward right. Bergenin also suppressed the PE peak formation, indicating the antagonist effect against the release of Ca2+. Moreover, the bergenin-induced vasorelaxant response was not markedly attenuated with TEA, while significantly ablated with 4-AP and BaCl2. In conclusion, the antihypertensive effects of bergenin are due to Ca2+ channel blockade, K+ channels activation, and muscarinic receptor-linked vasodilation.

The association of dietary glutamine supplementation with the development of high salt-induced hypertension in rats.

Glutamine supplementation has been reported to affect blood pressure (BP). However, its role in the progression of hypertension induced by high salt diet (HSD) has not been elucidated. Male normotensive Wistar rats were exposed to high salt diet and treated with different doses of glutamine supplementation. Rats aged 6 weeks were assigned to five groups: (1) Normal-salt diet (0.3% NaCl, NSD); (2) High-salt diet (8% NaCl, HSD); (3) High-salt + low-dose diet (8% NaCl, 0.5 g of L-glutamine/kg body weight, HSLGD); (4) High-salt + middle-dose diet (8% NaCl, 1.5 g of L-glutamine/kg body weight, HSMGD); and (5) High-salt + high-dose diet (8% NaCl, 2.5 g of L-glutamine/kg body weight, HSHGD). After supplementing different doses of glutamine to male Wistar 6-week-old rats fed with HSD for 7 weeks, we found no difference in body weight among groups. Importantly, we showed that dietary L-glutamine supplementation could prevent the development of hypertension in a dose-dependent manner [dramatically lowering systolic blood pressure (SBP) and slightly reducing diastolic blood pressure (DBP) of hypertensive rats, while the differences of DBP between groups did not reach statistical significance]. Our data further elucidated that dietary glutamine supplementation mildly alleviated the degree of left ventricular hypertrophy, including interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in hypertensive rats. Together, our results offer evidence that the dietary uptake of glutamine may be associated with attenuating the development of high salt-induced hypertension and slightly alleviating the degree of left ventricular hypertrophy in hypertensive rats. Therefore, glutamine supplementation may act as a prospective dietary intervention for the treatment of hypertension.

Antihypertensive Effects of Aqueous Extract of Ricinodendron heudelotii (Baill.) Pierre (Euphorbiaceae) in Wistar Rat.

Ricinodendron heudelotii stem bark is commonly used in Cameroonian traditional medicine to treat cardiovascular diseases such as hypertension. The present study was designed to investigate the antihypertensive and antioxidant properties of the aqueous extract of Ricinodendron heudelotii in salt-induced hypertensive rats. Analysis by HPLC-ESI-Q-TOF-MS was used to identify various chemical components of the extract. A total of thirty rats were used for each test. High-salt hypertension was induced in rats by oral administration of NaCl for 12 weeks. Mean blood pressure (MBP) and heart rate (HR) were monitored by noninvasive methods. Oral administration of Ricinodendron heudelotii significantly (p < 0.01) reduced the increase of mean blood pressure (23.12%, 26.14%, and 24.34%) and heart rate (31.19%, 31.09%, and 26.98%), respectively, at the doses of 40, 20, and 6 mg/kg, compared to the hypertensive group. All the doses tested significantly reduced or/and ameliorated biochemical and oxidative stress parameters. Histological analysis showed that Ricinodendron heudelotii restored renal disorders induced by the administration of salt. The aqueous extract of Ricinodendron heudelotii exerts a cardioprotective effect, and the antihypertensive activity seems associated with an improvement in antioxidant status. Overall, the results justify and support the traditional use of Ricinodendron heudelotii.

MiRNA-23a modulates sodium-hydrogen exchanger 1 expression: studies in medullary thick ascending limb of salt-induced hypertensive rats.

The kidney is the main organ in the pathophysiology of essential hypertension. Although most bicarbonate reabsorption occurs in the proximal tubule, the medullary thick ascending limb (mTAL) of the nephron also maintains acid-base balance by contributing to 25% of bicarbonate reabsorption. A crucial element in this regulation is the sodium-hydrogen exchanger 1 (NHE1), a ubiquitous membrane protein controlling intracellular pH, where proton extrusion is driven by the inward sodium flux. MicroRNA (miRNA) expression of hypertensive patients significantly differs from that of normotensive subjects. The aim of this study was to determine the functional role of miRNA alterations at the mTAL level. By miRNA microarray analysis, we identified miRNA expression profiles in isolated mTALs from high sodium intake-induced hypertensive rats (HSD) versus their normotensive counterparts (NSD). In vitro validation was carried out in rat mTAL cells. Five miRNAs involved in the onset of salt-sensitive hypertension were identified, including miR-23a, which was bioinformatically predicted to target NHE1 mRNA. Data demonstrated that miRNA-23a is downregulated in the mTAL of HSD rats while NHE1 is upregulated. Consistently, transfection of an miRNA-23a mimic in an mTAL cell line, using a viral vector, resulted in NHE1 downregulation. NHE1, a protein involved in sodium reabsorption at the mTAL level and blood pressure regulation, is upregulated in our model. This was due to a downregulation of miRNA-23a. Expression levels of this miRNA are influenced by high sodium intake in the mTALs of rats. The downregulation of miRNA-23a in humans affected by essential hypertension corroborate our data and point to the potential role of miRNA-23a in the regulation of mTAL function following high salt intake.

Measurement of Hemodynamic Parameters and Antidepressant Activity in Hypertensive Rats Following Two Weeks Consumption of Acacia Tortilis Leaves Extract

Background: Depression is common in hypertensive patients, and monotherapy may contribute to controlling depression in hypertensive patients and improving socioeconomic outcomes. Previous studies have shown that Acacia tortilis possesses hypotensive activity. Objectives: The present study was planned to evaluate the hemodynamic activity and antidepressant effects of an ethanolic extract of Acacia tortilis leaves (ATEL) in salt-induced hypertensive rats. Methods: Sprague-Dawley rats were divided into 5 groups for experiments. The rats received respective treatment for 15 days: G1: Control (C); G2: hypertensive control (HC: high dietary salt, 4% 10ml/kg); G3-5: HC+ ATEL (50, 100, 150mg/kg respectively). Cardiac hemodynamics (mean arterial blood pressure: MAP and heart rate: HR) were measured in the anaesthetized rats by an invasive method. For this method, one carotid artery was catheterized, a pressure catheter (pressure- volume Millar microtip catheter connected to the Mikro-Tip Pressure-Volume System from Ultra Foundation Systems, PowerLab) was inserted, and the blood pressure (MAP in mm Hg) and HR (beats/min) were monitored continuously during the experiment. For the neuropharmacological studies, antidepressant activity was assessed by a forced swim test on the 15th day. Results: A dose-dependent significant increase in mobility time was observed in rats (G3-5) treated with HC + different doses of ATEL (p &lt; 0.05). However, the mobility time was significantly reduced by HC (G2) treatment compared to the control (p&lt; 0.05). The hypertensive control (high dietary salt: HC) group showed a significant increase in systolic blood pressure (SP), diastolic blood pressure (DP), MAP and HR (p&lt;0.05) compared to the control (G1) group. At all doses (50, 100, and 150 mg/kg), MAP and HR were found to decrease significantly (p&lt;0.05) compared to the values in the HC (G2) group. Further analysis revealed an improvement in heart rate variability (HRV) in ATEL-treated hypertensive rats. Conclusion: The present research suggests that increased dietary salt intake not only increases blood pressure significantly but also increases depression. ATEL contains some efficacious constituents, such as N, N-dimethyltryptamine (DMT: a 5-HT1A agonist), with predominant antidepressant and antihypertensive activity. Hence, ATEL appears to be a valuable plant extract that can be useful, at least as an adjunct, for therapy in patients who suffer from both depression and hypertension.

Antihypertensive Activity in High Salt-Induced Hypertensive Rats and LC-MS/MS-Based Phytochemical Profiling of Melia azedarach L. (Meliaceae) Leaves.

Melia azedarach L. leaves have been traditionally used but not scientifically evaluated for antihypertensive activity. The focus of the present work was to carry out the detailed phytochemical profiling and antihypertensive potential of methanolic extract and subsequent fractions of this plant. The tandem mass spectrometry-based phytochemical profiling of M. azedarach extract (Ma.Cr) and fractions was determined in negative ionization mode while molecular networking was executed using the Global Natural Product Social (GNPS) molecular networking platform. This study resulted in the identification of 29 compounds including flavonoid O-glycosides, simple flavonoids, triterpenoidal saponins, and cardenolides as the major constituents. Ma.Cr at the concentration of 300 mg/kg resulted in a fall in blood pressure (BP), i.e., 81.44 ± 2.1 mmHg in high salt-induced hypertensive rats in vivo, in comparison to normotensive group, i.e., 65.36 ± 1.8 mmHg at the same dose. A decrease in blood pressure was observed in anaesthetized normotensive and hypertensive rats treated with extract and various fractions of M. azedarach. A reasonable activity was observed for all fractions except the aqueous fraction. The highest efficacy was shown by the ethyl acetate fraction, i.e., 77.06 ± 3.77 mmHg in normotensive and 88.96 ± 1.3 mmHg in hypertensive anaesthetized rats. Ma.Cr and fractions showed comparatively better efficacy towards hypertensive rats as compared to rats with normal blood pressure. Blood pressure-lowering effects did not change upon prior incubation with atropine. In vitro testing of Ma.Cr and polarity-based fractions resulted in L-NAME sensitive, endothelium-dependent vasodilator effects on aortic tissues. Pretreatment of aorta preparations with Ma.Cr and its fractions also blocked K+-induced precontractions indicating Ca2+ channel blocking activity comparable to verapamil. The extract and polarity-based fractions did not reveal a vasoconstrictor response in spontaneously beating isolated rat aorta. Ma.Cr and fractions when used in atrial preparations resulted in negative inotropic and chronotropic effects. These effects in atrial preparations did not change in the presence of atropine. These effects of extract and fractions explained the antihypertensive potential of M. azedarach and thus provided a scientific basis for its ethnopharmacological use in the treatment of hypertension. Among the constituents observed, flavonoids and flavonoid O-glycosides were previously reported for antihypertensive potential.

Anti-Hypertensive Effects of Anthocyanins from Hibiscus sabdarifa Calyx on the Renin-Angiotensin-Aldoslestrone System in Wistar Rats.

Hibiscus sabdariffa (HS) has gained attention as an anti-hypertensive agent. In the present study, we hypothesized that anthocyanins from HS may attenuate salt-induced hypertension in rats by suppressing the components of renin-angiotensin-aldoslestrone system (RAAS). Hypertension was induced in the rats by adding 8% NaCl in their diet for six weeks. Wistar rats (n=5 each) were randomly divided into seven groups. Group 1 was the normentensive control group and was fed with normal rat chew and water ad libitum; groups 2 and 3 served as hypertensive control (negative untreated and positive treated with captopril 30mg/kg respectively); groups 4, 5, and 6 served as treatment groups and were administered with graded doses of anthocyanins( 50, 100, 200mg/kg respectively) while group 7 received both 100mg anthocyanins and 30mg captopril per day for 4 weeks. Using HPLC, anthocyanins were isolated from HS calyx following standard protocol. Anthocyanins significantly (p<0.05) reduced blood pressure and heart rate in hypertensive rats in a dose dependent manner. The blood pressure reduction by anthocyanins was associated with a reduction in serum ACE and plasma aldosterone in the hypertensive rats. The effects of anthocyanins on blood pressure and on biomarkers of RAAS were similar to those of captopril, a reference anti-hypertensive drug. The results suggest that anthocyanins exerts a significant (p<0.05) anti-hypertensive potency on rats, probably mediated by the reduction in components of the RAAS. Keywords: hypertension, anthocyanins, renin, aldosterone, rats.

In vitro, in vivo and stability assessment of optimised nanoparticulate matrix tablet of nebivolol hydrochloride

The objective of the present study was to define the effects on the antihypertension activity and pharmacokinetics of an optimised nanoparticulate matrix tablet containing nebivolol hydrochloride. The nanoparticulate matrix tablet was formulated using Nebivolol nanoparticles which are prepared by a solvent evaporation method using varying concentrations of drug and polymer Eudragit RL 100 and optimised by two factorial designs using a quadratic model and the nanoparticulate matrix tablet was prepared by using a varying concentration of drug nanoparticles and ethyl cellulose. The sustained release ability formulation was further demonstrated in an in-vivo study in Wister rats. The prepared matrix tablets showed an improved bioavailability. The Tmax, Cmax, and the AUC were increased and extended, respectively. The antihypertensive activity showed a distinct change in SBP in DOCA salt-induced hypertensive rats as compared with pure drug. A significant reduction of DBP and HR were also observed after the treatment with nanoparticulate matrix tablet. There was no significant degradation and change in drug release rate in formulations during six months of stability testing. The results suggest that nanoparticulate matrix tablets can act as a promising carrier for nebivolol hydrochloride which offers an alternative approach for regular delivery of nebivolol.

Early cardiac-chamber-specific fingerprints in heart failure with preserved ejection fraction detected by FTIR and Raman spectroscopic techniques

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is a matter of investigation and its diagnosis remains challenging. Although the mechanisms that are responsible for the development of HFpEF are not fully understood, it is well known that nearly 80% of patients with HFpEF have concomitant hypertension. We investigated whether early biochemical alterations were detectable during HFpEF progression in salt-induced hypertensive rats, using Fourier-transformed infrared (FTIR) and Raman spectroscopic techniques as a new diagnostic approach. Greater protein content and, specifically, greater collagen deposition were observed in the left atrium and right ventricle of hypertensive rats, together with altered metabolism of myocytes. Additionally, Raman spectra indicated a conformational change, or different degree of phosphorylation/methylation, in tyrosine-rich proteins. A correlation was found between tyrosine content and cardiac fibrosis of both right and left ventricles. Microcalcifications were detected in the left and right atria of control animals, with a progressive augmentation from six to 22 weeks. A further increase occurred in the left ventricle and right atrium of 22-week salt-fed animals, and a positive correlation was shown between the mineral deposits and the cardiac size of the left ventricle. Overall, FTIR and Raman techniques proved to be sensitive to early biochemical changes in HFpEF and preceded clinical humoral and imaging markers.

Na+/K+-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension.

Numerous studies have indicated that a high salt diet inhibits brain Na+/K+-ATPase (NKA) activity, and affects oxidative stress and inflammation in the paraventricular nucleus (PVN). Furthermore, Na+/K+-ATPase alpha 2-isoform (NKA α2) may be a target in the brain, taking part in the development of salt-dependent hypertension. Therefore, we hypothesized that NKA α2 regulates oxidative stress and inflammation in the PVN in the context of salt-induced hypertension. Part I: We assessed NKA subunits (NKA α1, NKA α2, and NKA α3), Na+/K+-ATPase activity, oxidative stress, and inflammation in a high salt group (8% NaCl) and normal salt group (0.3% NaCl). Part II: NKA α2 short hairpin RNA (shRNA) was bilaterally microinjected into the PVN of salt-induced hypertensive rats to knockdown NKA α2, and we explored whether NKA α2 regulates downstream signaling pathways related to protein kinase C γ (PKC γ)-dependent oxidative stress and toll-like receptor 4 (TLR4)-induced inflammation in the PVN to promote the development of hypertension. High salt diet increased NKA α1 and NKA α2 protein expression in the PVN but had no effect on NKA α3 compared to the normal salt diet. Na+/K+-ATPase activity and ADP/ATP ratio was lower, but NAD(P)H activity and NF-κB activity in the PVN were higher after a high salt diet. Bilateral PVN microinjection of NKA α2 shRNA not only improved Na+/K+-ATPase activity and ADP/ATP ratio but also suppressed PKC γ-dependent oxidative stress and TLR4-dependent inflammation in the PVN, thus decreasing sympathetic activity in rats with salt-induced hypertension. NKA α2 in the PVN elicits PKC γ/Rac1/NAD (P)H-dependent oxidative stress and TLR4/MyD88/NF-κB-induced inflammation in the PVN, thus increasing MAP and sympathetic activity during the development of salt-induced hypertension.

Effects of Methanol Fraction of Anarcardium Occidentale (Cashew) Bark Extract on SaltInduced Hypertension in Rats

Background: Hypertension is an important public health problem that needs multiple treatment approach. Anacardium occidentale Linn. (Anacardiaceae) on the other hand is a plant largely used locally in for treatment of various ailments. The present study therefore assessed the antihypertensive effects of methanol extract of Anacardium occidentale (AO) root back on cardiovascular parameters in high salt fed Wistar rats

Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats.

Aims: Long-term salt diet induces the oxidative stress in the paraventricular nucleus (PVN) and increases the blood pressure. Extracellular superoxide dismutase (Ec-SOD) is a unique antioxidant enzyme that exists in extracellular space and plays an essential role in scavenging excessive reactive oxygen species (ROS). However, the underlying mechanism of Ec-SOD in the PVN remains unclear. Methods: Sprague–Dawley rats (150–200 g) were fed either a high salt diet (8% NaCl, HS) or normal salt diet (0.9% NaCl, NS) for 6 weeks. Each group of rats was administered with bilateral PVN microinjection of AAV-Ec-SOD (Ec-SOD overexpression) or AAV-Ctrl for the next 6 weeks. Results: High salt intake not only increased mean arterial blood pressure (MAP) and the plasma noradrenaline (NE) but also elevated the NAD(P)H oxidase activity, the NAD(P)H oxidase components (NOX2 and NOX4) expression, and ROS production in the PVN. Meanwhile, the NOD-like receptor protein 3 (NLRP3)–dependent inflammatory proteins (ASC, pro-cas-1, IL-β, CXCR, CCL2) expression and the tyrosine hydroxylase (TH) expression in the PVN with high salt diet were higher, but the GSH level, Ec-SOD activity, GAD67 expression, and GABA level were lower than the NS group. Bilateral PVN microinjection of AAV-Ec-SOD decreased MAP and the plasma NE, reduced NAD(P)H oxidase activity, the NOX2 and NOX4 expression, and ROS production, attenuated NLRP3-dependent inflammatory expression and TH, but increased GSH level, Ec-SOD activity, GAD67 expression, and GABA level in the PVN compared with the high salt group. Conclusion: Excessive salt intake not only activates oxidative stress but also induces the NLRP3-depensent inflammation and breaks the balance between inhibitory and excitability neurotransmitters in the PVN. Ec-SOD, as an essential anti-oxidative enzyme, eliminates the ROS in the PVN and decreases the blood pressure, probably through inhibiting the NLRP3-dependent inflammation and improving the excitatory neurotransmitter release in the PVN in the salt-induced hypertension.

F2-Isoprostane Levels in Deoxycorticosterone Acetate (DOCA)-Salt Induced Hypertensive Rats Administered with Coffee-Corn Mixture

The purpose of this study is to analyze F2-Isoprostane levels in Deoxycorticosterone Acetate (DOCA)–Salt induced hypertensive rats that is given Coffee-Corn mixture. Measurement of blood pressure was carried out by non-invasive methods using CODA instruments. The coffee-corn mixture was made from Robusta (Coffea canephora) obtained from Kaliwining, Jember Regency, and Yellow Corn (Zea Mays) bought from the local market in Jember, East Java, Indonesia. F2-Isoprostane levels were obtained by ELISA examination. The mice’s blood pressure was measured using a non-invasive CODA® blood pressure gauge. Serum F2-isoprostane levels were measured using an F2-isoprostane-ELISA kit that was read with an Elisa reader at a wavelength of 450nm. The results showed that there was a decrease in mean systolic blood pressure in each treatment group, with the most decrease by 41.88mmHg occured in the group that was given a coffee-corn mixture with a ratio of 50% Robusta coffee (Coffea canephora) Kaliwining and 50% yellow corn (Zea Mays). The highest decrease in diastolic blood pressure by 35.25mmHg was also attained in the same group. From the results of serum F2 isoprostrane level examination, there was a decrease in the average level of serum F2 isoprostrane in the treatment group with the most reduction by 51.34pg/mL occured in the group given a coffee-corn mixture with a ratio of 50% Robusta (Coffea canephora) Kaliwining and 50% yellow maize (Zea Mays). Coffee-corn mixture can reduce blood pressure in hypertensive mice through anti-oxidant effects.

Transfer RNA Fragments in the Kidney in Hypertension.

[Figure: see text].

Preventive Beneficial Effect of an Aqueous Extract of Phyllanthus amarus Schum. and Thonn. (Euphorbiaceae) on DOCA-Salt-Induced Hypertension, Cardiac Hypertrophy and Dysfunction, and Endothelial Dysfunction in Rats.

This study investigated the preventive effect of an aqueous extract of the whole plant of Phyllanthus amarus (AEPA) on blood pressure, cardiac, and endothelial function in the deoxycorticosterone acetate (DOCA) salt-induced hypertensive rat model. Male Wistar rats were assigned into 5 groups receiving either vehicle (control and DOCA salt), DOCA salt combined with AEPA at 100 or 300 mg/kg, or AEPA (100 mg/kg) alone for 5 weeks. In addition, DOCA salt-treated rats were allowed free access to water containing 1% NaCl. Systolic blood pressure, left ventricle parameters, vascular reactivity of primary mesenteric artery rings, the vascular level of oxidative stress, and the level of target proteins were determined, using respectively tail-cuff sphygmomanometry, echocardiography, organ chambers, dihydroethidium staining, and immunofluorescence methods. After 5 weeks, AEPA treatments (100 or 300 mg/kg per day) significantly prevented the increase in systolic blood pressure in DOCA salt-treated rats, respectively, by about 24 and 21 mm Hg, improved cardiac diastolic function, and reduced significantly the increased posterior and septum diastolic wall thickness and the left ventricle mass in hypertensive rats. Moreover, the DOCA salt-induced endothelial dysfunction and the blunted nitric oxide- and endothelium-dependent hyperpolarization-mediated relaxations in primary mesenteric artery were improved after the AEPA treatments. AEPA also reduced the level of vascular oxidative stress and the expression level of target proteins (eNOS, COX-2, NADPH oxidase subunit p22) in DOCA salt rats. Altogether, AEPA prevented hypertension, improved cardiac structure and function, and improved endothelial function in DOCA salt rats. Such beneficial effects seem to be related, at least in part, to normalization of the vascular level of oxidative stress.