Hypertension is a major controllable risk factor associated with cardiovascular disease (CVD) and overall mortality worldwide. Most people with hypertension must take medications that are effective in blood pressure management but cause many side effects. Thus, it is important to explore safer antihypertensive alternatives to regulate blood pressure. In this study, peanut protein concentrate (PPC) was hydrolyzed with 3-5% Alcalase for 3-10 h. The in vitro angiotensin-converting enzyme (ACE) and renin-inhibitory activities of the resulting peanut protein hydrolysate (PPH) samples and their fractions of different molecular weight ranges were determined as two measures of their antihypertensive potentials. The results show that the crude PPH produced at 4% Alcalase for 6 h of hydrolysis had the highest ACE-inhibitory activity with IC50 being 5.45 mg/mL. The PPH samples produced with 3-5% Alcalase hydrolysis for 6-8 h also displayed substantial renin-inhibitory activities, which is a great advantage over the animal protein-derived bioactive peptides or hydrolysate. Remarkably higher ACE- and renin-inhibitory activities were observed in fractions smaller than 5 kDa with IC50 being 0.85 and 1.78 mg/mL. Hence, the PPH and its small molecular fraction produced under proper Alcalase hydrolysis conditions have great potential to serve as a cost-effective anti-hypertensive ingredient for blood pressure management.

Both hypertension and aging are known to increase the vulnerability of the brain to neurovascular damage, resulting in cognitive impairment. The present study investigated the efficacy of the antihypertensive drug losartan on age- and hypertension-associated cognitive decline and the possible mechanism underlying its effect in spontaneously hypertensive rats (SHRs). Losartan was administered (10 mg/kg, i.p. for 19 days) to 3- and 14-month-old SHRs. Age-matched Wistar rats were used as controls. Working memory, short-term object recognition, and spatial memory were assessed using the Y-maze, object recognition test (ORT) and radial arm maze (RAM) test. The expression of markers associated with aging, oxidative stress, and memory-related signaling was assessed in the frontal cortex (FC) and hippocampus. Motor activity measured over 24 h was not different between groups. Middle-aged vehicle-treated SHRs showed poorer performance in spontaneous alternation behavior (SAB) and activity in the first Y-maze test than their younger counterparts, suggesting age-related reduced \"decision making\" and reactivity in a novel environment. Losartan improved the age- and hypertension-induced decline in short-term recognition and spatial memory measured in the ORT and the second Y-maze test, particularly in the middle-aged rats, but was ineffective in the young adult rats. Changes in memory and age-related markers such as cAMP response element-binding protein (CREB) and amyloid-β1-42 (Aβ1-42) and increased oxidative stress were observed in the hippocampus but not in the FC between young adult and middle-aged vehicle-treated SHRs. Losartan increased CREB expression while reducing Aβ1-42 levels and concomitant oxidative stress in middle-aged SHRs compared with vehicle-treated SHRs. In conclusion, our study highlights the complex interplay between hypertension, aging, and cognitive impairment. It suggests that there is a critical time window for therapeutic intervention with angiotensin II type 1 receptor blockers.

Background: Hypertension poses a significant global health burden and is associated with cardiovascular morbidity. Chios mastic gum (CMG), derived from Pistacia lentiscus var. Chia, shows potential as a phytotherapeutic agent, due to its multifaceted beneficial effects. However, its anti-hypertensive effects and vascular, circulatory, and renal-related dysfunction, have not been thoroughly investigated. Herein, we aimed to explore the antihypertensive potential of CMG, focusing on vascular and renal endothelium, in vivo. Methods: Two models of hypertension in male rats, induced by Angiotensin II and Deoxycorticosterone acetate (DOCA)-high-salt administration, were utilized. CMG was administered at 220 mg/kg daily for four weeks after hypertension onset and blood pressure was measured non-invasively. Whole blood RNA sequencing, metabolomics, real-time PCR, and Western blot analyses of kidney and aorta tissues were additionally performed. Results: CMG significantly lowered systolic, diastolic, and mean blood pressure in both models. RNA sequencing revealed that CMG modulated immunity in the Angiotensin II model and metabolism in the DOCA-HS model. CMG downregulated genes related to oxidative stress and endothelial dysfunction and upregulated endothelial markers such as Vegfa. Metabolomic analysis indicated improved endothelial homeostasis via lysophosphatidylinositol upregulation. Conclusions: CMG emerges as a potent natural antihypertensive therapy, demonstrating beneficial effects on blood pressure and renal endothelial function.

Resveratrol, acting as a prebiotic, and propionate, functioning as a postbiotic, hold promise for preventing hypertension in chronic kidney disease (CKD). Previously, we employed propionate to enhance the bioavailability of resveratrol through esterification, resulting in the production of a resveratrol propionate ester (RPE) mixture. In this study, we purified 3-O-propanoylresveratrol (RPE2) and 3,4\'-di-O-propanoylresveratrol (RPE4) and investigated their protective effects in a juvenile rat adenine-induced CKD model. To this end, male Sprague Dawley rats aged three weeks (n = 40) were divided into five groups: control; CKD (rats fed adenine); CKRSV (CKD rats treated with 50 mg/L resveratrol); CDRPE2 (CKD rats treated with 25 mg/L RPE2); and CKRPE4 (CKD rats treated with 25 mg/L RPE 4). RPE2 and PRE4 similarly exhibited blood pressure-lowering effects comparable to those of resveratrol, along with increased nitric oxide (NO) availability. Furthermore, RPE2 and RPE4 positively influenced plasma short-chain fatty acid (SCFA) levels and induced distinct alterations in the gut microbial composition of adenine-fed juvenile rats. The supplementation of RPE2 and RPE4, by restoring NO, elevating SCFAs, and modulating the gut microbiota, holds potential for ameliorating CKD-induced hypertension.

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This practice guideline was developed by the chronic kidney disease (CKD) Task Force, which was composed of clinical and methodological experts. The Saudi Arabian Ministry of Health and its health holding company commissioned this guideline project to support the realization of Vision 2030\'s health-care transformation pillar. The synthesis of these guidelines was guided by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)- ADOLOPMENT methodology. The final guidelines addressed 12 clinical questions on the management of blood pressure in patients with CKD through a set of recommen-dations and performance measures. The recom-mendations included antihypertensive agents in children; renin- angiotensin system inhibition (RASi) versus non-RASi in adults; intensive versus standard blood pressure targets; early versus late assessment for kidney replacement therapy (KRT); late versus early preparation strategies for KRT; CKD symptoms during assessment for KRT or conservative manage-ment; initiation of KRT in patients with deteriorating CKD; choice of KRT modality or conservative management in certain CKD patient groups; changing or discontinuing KRT modalities; the frequency of reviews for KRT or conservative management; and information, education, and support. These conditional recommendations were based on a low to very low certainty of evidence, which highlights the need for high-quality randomized trials com-paring different antihypertensive agents in patients with CKD.

Recently, the effect of an aqueous extract of asafetida on acute angiotensin II hypertensive rats was evaluated. The present study evaluated the antihypertensive and antioxidant effects of asafetida on a rat model of renovascular hypertension (RVH) using four groups. RVH was induced by clipping the renal artery; the sham group underwent surgery but without clipping. The RVH rats received losartan (Los, an AT1 receptor antagonist) or asafetida by gavage for 4 weeks. On the 28th day, the femoral artery was cannulated, and the systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were recorded. Finally, the levels of superoxide dismutase (SOD) activity, malondialdehyde (MDA), and total thiol content in the kidney and heart tissues were measured. In RVH rats, SBP and MAP significantly increased compared with the control. Los and the extract significantly reduced the changes in SBP, MAP, and HR that were induced in the RVH rats (P <0.05-0.001). In RVH rats, levels of MDA significantly increased and the content of total thiol and SOD decreased in both the heart and kidney tissues. Los plus the extract significantly decreased MDA and increased total thiol and SOD in the heart and kidney tissues. We concluded that an aqueous extract of asafetida gum has antihypertensive and antioxidant effects in the RVH rat model. The effect of the extract is similar to that of Los, which suggests that this effect of asafetida is mediated via an effect on the angiotensin Type I receptor.

BACKGROUND: Previous studies have shown that peptides encoded by noncoding RNAs (ncRNAs) can be used as peptide drugs to alleviate diseases. We found that microRNA-31 (miR-31) is involved in the regulation of hypertension and that the peptide miPEP31, which is encoded by the primary transcript of miR-31 (pri-miR-31), can inhibit miR-31 expression. However, the role and mechanism of miPEP31 in hypertension have not been elucidated.
METHODS: miPEP31 expression was determined by western blot analysis. miPEP31-deficient mice (miPEP31-/-) were used, and synthetic miPEP31 was injected into Ang II-induced hypertensive mice. Blood pressure was monitored through the tail-cuff method. Histological staining was used to evaluate renal damage. Regulatory T (Treg) cells were assessed by flow cytometry. Differentially expressed genes were analysed through RNA sequencing. The transcription factors were predicted by JASPAR. Luciferase reporter and electrophoretic mobility shift assays (EMSAs) were used to determine the effect of pri-miR-31 on the promoter activity of miPEP31. Images were taken to track the entry of miPEP31 into the cell.
RESULTS: miPEP31 is endogenously expressed in target organs and cells related to hypertension. miPEP31 deficiency exacerbated but exogenous miPEP31 administration mitigated the Ang II-induced systolic blood pressure (SBP) elevation, renal impairment and Treg cell decreases in the kidney. Moreover, miPEP31 deletion increased the expression of genes related to Ang II-induced renal fibrosis. miPEP31 inhibited the transcription of miR-31 and promoted Treg differentiation by occupying the Cebpα binding site. The minimal functional domain of miPEP31 was identified and shown to regulate miR-31.
CONCLUSIONS: miPEP31 was identified as a potential therapeutic peptide for treating hypertension by promoting Treg cell differentiation in vivo. Mechanistically, we found that miPEP31 acted as a transcriptional repressor to specifically inhibit miR-31 transcription by competitively occupying the Cebpα binding site in the pri-miR-31 promoter. Our study highlights the significant therapeutic effect of miPEP31 on hypertension and provides novel insight into the role and mechanism of miPEPs.

BACKGROUND: Glaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent β-blocker.
METHODS: Of these, 176 patients used a β-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent β-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan-Meier survival analysis.
RESULTS: Allergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent β-blocker-usage groups, respectively. Kaplan-Meier survival analysis indicated that half of the allergies in the concurrent β-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent β-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent β-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent β-blocker-usage group.
CONCLUSIONS: Concurrent use of β-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of β-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education.