scholarly journals Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1404
Author(s):  
Saori Deguchi ◽  
Fumihiko Ogata ◽  
Masaki Watanabe ◽  
Hiroko Otake ◽  
Naoki Yamamoto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intestinal Absorption ◽  
Antihypertensive Effect ◽  
The Other ◽  
Drug Solubility ◽  
Inclusion Complex Formation ◽  
Significant Information ◽  
Spontaneously Hypertensive ◽  
Bead Mill ◽  
The Mean

We attempted to design irbesartan nanocrystalline (IRB-NC) suspensions by the bead mill method, and we evaluated the bioavailability (BA) in the oral administration of the nanocrystalline drug. The mean particle size of the IRB-NC suspensions was approximately 140 nm, and the crystalline structure of irbesartan in these suspensions was different using the bead mill method. The aggregation and degradation of irbesartan were not observed for one month, and the solubility increased. Moreover, the inclusion complex formation of IRB-NC suspensions with 2-hydroxypropyl-β-cyclodextrin was higher than that in traditional IRB powder (IRB-P). In addition, the intestinal absorption of IRB-NC suspensions was higher than that of IRB-P suspensions, and the reducing effect on blood pressure in spontaneously hypertensive SHR-SP rats orally administered IRB-NC suspensions was significantly higher than in those administered IRB-P suspensions. On the other hand, the intestinal penetration of IRB-NC suspensions was attenuated by the inhibitors of clathrin-dependent endocytosis (CME). In conclusion, we improved the low oral BA of irbesartan by preparing IRB-NC suspensions and showed that both the solubility and CME are related to the enhanced intestinal absorption of IRB-NC suspensions, resulting in an increase in their antihypertensive effect. These findings provide significant information for the development of oral nanomedicines.

scholarly journals Blood Pressure-Lowering Effect of Wine Lees Phenolic Compounds Is Mediated by Endothelial-Derived Factors: Role of Sirtuin 1

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1073
Author(s):  
Raúl López-Fernández-Sobrino ◽  
Jorge R. Soliz-Rueda ◽  
Javier Ávila-Román ◽  
Anna Arola-Arnal ◽  
Manuel Suárez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Sirtuin 1 ◽  
Dependent Manner ◽  
Blood Pressure Lowering Effect ◽  
Synthesis Inhibitor ◽  
Spontaneously Hypertensive ◽  
Lowering Effect ◽  
Pressure Lowering ◽  
Endothelial Gene Expression

The antihypertensive effect of wine lees powder (WLPW) from a Cabernet grape variety was related to its high content in flavanols and anthocyanins compounds. This study investigates the involvement of endothelial-derived factors and SIRT1 in its bioactivity. Spontaneously hypertensive rats (SHR) were orally administered water or WLPW (125 mg/kg bw). Posteriorly, both groups were intraperitoneally administered saline, Nω-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthesis inhibitor, indomethacin, a prostacyclin synthesis inhibitor, or sirtinol, an inhibitor of sirtuins. Blood pressure (BP) was recorded before and 6 h after WLPW administration. In an additional experiment, SHR were administered water or WLPW and endothelial expressions of eNos, Sirt1, Nox4, and Et1 were determined. The BP-lowering properties of WLPW were abolished by L-NAME and partially reduced by indomethacin, demonstrating that WLPW antihypertensive effect was mediated by changes in NO availability, although prostacyclin also contributed to this activity. Moreover, BP-lowering effect was reduced by sirtinol, indicating that WLPW decreased BP in a SIRT1-dependent manner. Furthermore, WLPW upregulated eNos and Sirt1 and downregulated Nox4 and Et1 endothelial gene expression. These results evidence the vasoprotective effect of WLPW and show that its antihypertensive effect in SHR is endothelium dependent and mediated by SIRT1.

scholarly journals Antihypertensive Effect of Amaranth Hydrolysate Is Comparable to the Effect of Low-Intensity Physical Activity

2020 ◽  
Vol 10 (16) ◽  
pp. 5706
Author(s):  
Francisco Cabrera-Chávez ◽  
Veronica Lopez-Teros ◽  
Perla Yareli Gutiérrez-Arzapalo ◽  
Feliznando Isidro Cárdenas-Torres ◽  
Efren Rafael Rios-Burgueño ◽  
...  
Keyword(s):  
Physical Activity ◽  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Protein Hydrolysate ◽  
Spontaneously Hypertensive ◽  
Low Intensity ◽  
Average Group ◽  
Intensity Physical Activity ◽  
The Impact ◽  
Antihypertensive Peptides

Background and objectives: Both antihypertensive peptide intake and physical activity help to control blood pressure. Our aim was to evaluate the impact of consuming amaranth antihypertensive peptides on systolic blood pressure (SBP) in normotensive rats and the magnitude and relevance of the peptide-induced antihypertensive effect in spontaneously hypertensive rats (SHR). Materials and Methods: Treatments (alcalase-generated amaranth protein hydrolysate, captopril, or water) were given by gavage and the SBP measured by the tail-cuff method. Physical activity was performed five days/week (for twenty weeks). Results: The normotensive rats’ SBP (mmHg, average/group) remained unaffected after amaranth antihypertensive peptide supplementation (121.8) (p > 0.05 vs controls). In SHR, the SBP was lowered by 24.6 (sedentary/supplemented at two weeks), 42.0 (sedentary/supplemented at eight weeks), and 31.5 (exercised/non-supplemented at eight weeks) (p < 0.05 vs sedentary/non-supplemented). The combination of supplementation and physical activity lowered the SBP by 36.2 and 42.7 (supplemented/exercised at two weeks and eight weeks, respectively) (p < 0.05 vs sedentary/non-supplemented), but it did not have additional antihypertensive benefits (p > 0.05 vs sedentary/supplemented at eight weeks or exercised/non-supplemented at eight weeks). Conclusions: Amaranth antihypertensive peptide supplementation has no impact on SBP in normotensive rats. This supplementation develops sustained antihypertensive benefits in SHR, which are similar to the antihypertensive effect developed after eight- or twenty-week low-intensity physical activity. These findings have implications for developing safe and effective peptide-based functional foods.

Experiences with Metoprolol Durules®, A Slow-Release Formulation in Hypertension

1980 ◽  
Vol 8 (1) ◽  
pp. 44-49 ◽  
Author(s):  
Jaakko Tuomilehto ◽  
Aulikki Nissinen
Keyword(s):  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Moderate Hypertension ◽  
Antihypertensive Effect ◽  
Slow Release ◽  
Final Dose ◽  
Release Formulation ◽  
Once Daily ◽  
Slow Release Formulation ◽  
The Mean

The antihypertensive effect and the tolerability of metoprolol Durules® have been studied in fifty-five patients with mild to moderate hypertension. The patients' diastolic blood pressure was ≥95 mm Hg in order to qualify for entry. Thirty-seven out of fifty-three patients completing the study (70%) were treated with metoprolol Durules® monotherapy throughout the study. The mean blood pressure was reduced from 153/101 to 138/92 mm Hg after metoprolol Durules® compared to placebo (p < 0.001). Twenty-seven patients received one Durules® daily and ten patients received two Durules® daily as the final dose. Of the sixteen patients not responding on metoprolol Durules®, six patients achieved satisfactory control, i.e. a diastolic blood pressure below 95 mm Hg, when given 200 mg metoprolol + 25 mg hydrochlorothiazide (HCT). The results indicate that most patients with, mild or moderate hypertension can be controlled with metoprolol Durules® monotherapy given once daily. The addition of HCT gives a significant benefit in moderate hypertension, where metoprolol monotherapy is not sufficient.

scholarly journals Antihypertensive Effect of Radix Paeoniae Alba in Spontaneously Hypertensive Rats and Excessive Alcohol Intake and High Fat Diet Induced Hypertensive Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Chen Su-Hong ◽  
Chen Qi ◽  
Li Bo ◽  
Gao Jian-Li ◽  
Su Jie ◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Fat Diet ◽  
Spontaneously Hypertensive Rats ◽  
Antihypertensive Effect ◽  
Hdl Cholesterol ◽  
High Fat ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Excessive Alcohol ◽  
Radix Paeoniae Alba

Radix Paeoniae Alba (Baishao, RPA) has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD-) induced hypertensive rats and spontaneously hypertensive rats (SHR) was constantly received either RPA extract (25 or 75 mg/kg) or captopril (15 mg/kg) all along the experiments. As a result, RPA extract (75 mg/kg) could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT) and aspartate transaminase (AST) in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO) and endothelin (ET) levels.

Bioactive Peptides from Low Denatured Peanut Dregs: Production and Antihypertensive Activity

2011 ◽  
Vol 343-344 ◽  
pp. 698-706
Author(s):  
Yu Hao Zhang ◽  
Liang Ma ◽  
Qiang Wang
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Antihypertensive Activity ◽  
Gel Chromatography ◽  
Spontaneously Hypertensive ◽  
Peptide Fraction ◽  
Low Blood Pressure ◽  
Industrial Use ◽  
Peanut Proteins ◽  
Increased Activity

Hydrolysates of peanut protein from low denatured peanut dregs, which inhibit the angiotensinⅠconverting enzyme (ACE) were prepared by enzymic hydrolysis with Alcalase and N120p that are two proteases available for industrial use. Combination of Alcalase and N120p hydrolyzed peanut proteins most efficiently and the hydrolysates showed the most high activity (IC50=0.548 mg/ml). Sequential ultrafiltration of the hydrolysates with MW cut-off 10, 5 and 1KD resulted in increased activity of each filtrate up to IC50 of 0.255 mg/ml. Sephadex G-15 gel chromatography of the oligopeptides below MW 1KD eluted a peptide fraction of the most potent activity (IC50=0.091 mg/ml). the oligopeptide below MW 1 KD competitively inhibited ACE and it was evaluated for antihypertensive effect in spontaneously hypertensive rats (SHRs) following oral administration. Systolic blood pressure (SBP) significantly decreased after peptide ingestion and higher dose of peanut oligopeptides could not induce occurrence of low blood pressure.

Comparison of the effectiveness of captopril and olmesartan in hypertensive patients

2021 ◽  
pp. 97-100
Keyword(s):  
Blood Pressure ◽  
Emergency Services ◽  
Rest Period ◽  
Organ Damage ◽  
The Other ◽  
Pressure Measurements ◽  
Hypertensive Patients ◽  
Mortality And Morbidity ◽  
The Mean ◽  
The Difference

Purpose: Hypertensive conditions are situations that require immediate intervention in emergency services. Captopril is one of the most commonly used drugs in patients presenting to emergency departments with high blood pressure. In this study; we aimed to find an answer to the question of whether orally administered olmesartan could be an alternative to captopril in urgent hypertensive situations. Material and Method: In this study, blood pressure measurements were made after a 5-minute rest period in patients who presented to the emergency department of our hospital with the diagnosis of hypertension. Patients with a blood pressure of 180/100 mmHg and above and no signs of end-organ damage were followed up. Forty patients were given sublingual captopril 25 mg, and the other 40 patients were given 40 mg of olmesartan, and they were allowed to swallow the drug with some water. Afterward, the patients were followed for 3 hours (with blood pressure and pulse measurements), and their blood pressure was measured and recorded at five-minute intervals. Results: The mean age of the patients receiving captopril was 60.70±11.43 years, and the mean age of the patients receiving olmesartan was 57.02±13.86 years. Of the patients receiving captopril, 19 (57.5%) were male, 21 (52.5%) were female, 17 (42.5%) of the patients receiving olmesartan were male and 23 (57.5%) were female. In this study, patients treated with captopril and olmesartan were monitored for 3 hours and the differences between them in pulse and blood pressure measurements were evaluated. When the systolic blood pressures were compared, the difference at the tenth minute was significant, but the difference between the other minutes was not significant. Differences in diastolic blood pressure and heart rate were not significant. Conclusion: Oral administration of olmesartan in emergency hypertensive patients may be an alternative to captopril due to its effectiveness in reducing mortality and morbidity.

scholarly journals Involvement of Endocytosis in the Transdermal Penetration Mechanism of Ketoprofen Nanoparticles

2018 ◽  
Vol 19 (7) ◽  
pp. 2138 ◽  
Author(s):  
Noriaki Nagai ◽  
Fumihiko Ogata ◽  
Miyu Ishii ◽  
Yuya Fukuoka ◽  
Hiroko Otake ◽  
...  
Keyword(s):  
Skin Penetration ◽  
Cytochalasin D ◽  
Significant Information ◽  
Bead Mill ◽  
Penetration Mechanism ◽  
Auc Value ◽  
The Mean ◽  
Transdermal Penetration ◽  
Energy Dependent ◽  
Transdermal Formulation

We previously designed a novel transdermal formulation containing ketoprofen solid nanoparticles (KET-NPs formulation), and showed that the skin penetration from the KET-NPs formulation was higher than that of a transdermal formulation containing ketoprofen microparticles (KET-MPs formulation). However, the precise mechanism for the skin penetration from the KET-NPs formulation was not clear. In this study we investigated whether energy-dependent endocytosis relates to the transdermal delivery from a 1.5% KET-NPs formulation. Transdermal formulations were prepared by a bead mill method using additives including methylcellulose and carbopol 934. The mean particle size of the ketoprofen nanoparticles was 98.3 nm. Four inhibitors of endocytosis dissolved in 0.5% DMSO (54 μM nystatin, a caveolae-mediated endocytosis inhibitor; 40 μM dynasore, a clathrin-mediated endocytosis inhibitor; 2 μM rottlerin, a macropinocytosis inhibitor; 10 μM cytochalasin D, a phagocytosis inhibitor) were used in this study. In the transdermal penetration study using a Franz diffusion cell, skin penetration through rat skin treated with cytochalasin D was similar to the control (DMSO) group. In contrast to the results for cytochalasin D, skin penetration from the KET-NPs formulation was significantly decreased by treatment with nystatin, dynasore or rottlerin with penetrated ketoprofen concentration-time curves (AUC) values 65%, 69% and 73% of control, respectively. Furthermore, multi-treatment with all three inhibitors (nystatin, dynasore and rottlerin) strongly suppressed the skin penetration from the KET-NPs formulation with an AUC value 13.4% that of the control. In conclusion, we found that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis are all related to the skin penetration from the KET-NPs formulation. These findings provide significant information for the design of nanomedicines in transdermal formulations.

Blood pressure reducing effects of Phalaris canariensis in normotensive and spontaneously hypertensive rats

2012 ◽  
Vol 90 (2) ◽  
pp. 201-208 ◽  
Author(s):  
Clévia Santos Passos ◽  
Lucimeire Nova Carvalho ◽  
Roberto Braz Pontes ◽  
Ruy Ribeiro Campos ◽  
Olinda Ikuta ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Agent ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Antihypertensive Effect ◽  
Treatment Interruption ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Baseline Levels ◽  
Phalaris Canariensis

The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHRY, 3 weeks old). Animals received AEPc (400 mg·kg–1·day–1, by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHRY became hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHRY, but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na+ excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kinurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus.

scholarly journals Serum Metabolomics Study Based on LC-MS and Antihypertensive Effect of Uncaria on Spontaneously Hypertensive Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ana Liu ◽  
Yan-Jun Chu ◽  
Xiaoming Wang ◽  
Ruixue Yu ◽  
Haiqiang Jiang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Discriminant Analysis ◽  
Least Squares ◽  
Partial Least Squares ◽  
Antihypertensive Effect ◽  
Combination Method ◽  
Serum Samples ◽  
Multivariate Statistical ◽  
Spontaneously Hypertensive ◽  
Tof Ms

Our previous studies have shown that Uncaria has an important role in lowering blood pressure, but its intervention mechanism has not been clarified completely in the metabolic level. Therefore, in this study, a combination method of HPLC-TOF/MS-based metabolomics and multivariate statistical analyses was employed to explore the mechanism and evaluate the antihypertensive effect of Uncaria. Serum samples were analyzed and identified by HPLC-TOF/MS, while the acquired data was further processed by partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to discover the perturbed metabolites. A clear cluster among the different groups was obtained, and 7 significantly changed potential biomarkers were screened out. These biomarkers were mainly associated with lipid metabolism (dihydroceramide, ceramide, PC, LysoPC, and TXA2) and vitamin and amino acids metabolism (nicotinamide riboside, 5-HTP). The result indicated that Uncaria could decrease the blood pressure effectively, partially by regulating the above biomarkers and metabolic pathways. Analyzing and verifying the specific biomarkers, further understanding of the therapeutic mechanism and antihypertensive effect of Uncaria was acquired. Metabolomics provided a new insight into estimate of the therapeutic effect and dissection of the potential mechanisms of traditional Chinese medicine (TCM) in treating hypertension.

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