Antihypertensive Captopril Research Articles

Managing hypertension using brewing bioactive peptides as angiotensin-converting enzyme inhibitors: Impact on vascular tone through ex vivo assays

BackgroundPeptides derived from brewer’s spent grain (BSG) and yeast (BSY) are promising natural substitutes of synthetic drugs to manage hypertension as inhibitors of angiotensin-converting enzyme (ACE). However, their impact on the vascular function, so far, remains to be verified. Accordingly, we aimed to evaluate the effect of brewing peptides on the arterial vasocontractile response to angiotensin (Ang) I (through vascular ACE-inhibition) to estimate their antihypertensive potential. The impact of the oral route (gastrointestinal digestion, intestinal absorption, and liver metabolism) in brewing peptides was also investigated. MethodsIliac arteries from adult spontaneously hypertensive rats were studied with isometric tension recording. After ensuring the function integrity of the arteries, concentration-response curves to addition of Ang I (10−9-10−6 M) were performed after 30 min incubation with MIX (50:50 mixture of BSG:BSY) or BSG (0.86 mg/mL), or captopril (an ACE-inhibitory drug) or Krebs solution. ResultsMIX peptides (without simulated oral administration) enhanced Ang I-induced vasoconstriction, but lacked vascular effects after simulated oral administration. By contrast, BSG peptides (without simulated oral administration) did not exhibit vascular effects, whereas they promoted a marked decrease in vasocontraction evoked by the generated Ang II after simulation of the oral route, implying their capability to inhibit ACE. Additionally, to elucidate this inhibitory mechanism, Michaelis-Menten and Lineweaver-Burk plots indicated a mixed inhibition type. ConclusionWith simulation of the oral route, BSG peptides were able to inhibit vascular ACE with a similar efficacy as the antihypertensive drug captopril, suggesting the potential to mitigate the burden of hypertension.

Physicochemical investigation of encapsulation of antihypertensive drug captopril in mixed micellar system to enhance its delivery

This research work provides insight into the solubilization of a non-ionic drug captopril (CAP) in the micellar media of cationic surfactant cetyltrimethylammonium bromide (CTAB) and mixed micellar media of two nonionic surfactants Tween-80 and Triton X-100. CAP−surfactant interactions were analyzed by simple and differential absorption spectroscopy as well as by conductometry and the efficiency of the selected micellar system was assessed by calculating the values of partition coefficient (Kx), the free energy of partition (∆GP), binding constant (Kb) and the free energy of binding (∆Gb). Results from differential spectroscopy depicted a noteworthy increase in the solubilization of CAP with the addition of nonionic surfactants (Tween-80 and TX-100) in the micellar solution of CTAB. Furthermore, conductometric response of micellar media has been used to calculate the degree of dissociation (β), the free energy of micellization (∆Gm) thermodynamic parameters of micellization.

DETERMINATION OF THE ANTIHYPERTENSIVE DRUGS CAPTOPRIL, ATENOLOL, AND METOPROLOL IN DOSAGE FORMS

Three antihypertensive drugs Captopril (CPL), Atenolol (ATL), and Metoprolol (MTL) have been estimated sensitively and selectively by a single spectrophotometric method using neutral red dye NLR. The method is based on oxidation of the drugs by known excess of N-bromosuccinamide (NBS) in the first reaction step followed by the oxidation of NLR dye with the exceed ed amount of NBS, as the concentration of the drug compounds increase, the color of the dye increase, the dye exhibits absorbance peak at 523 nm. The linearity range was from 1 to 10 µg/ml for the three drugs, the molar absorptivity values were 2.1164 × 105, 1.9202× 104, and 57.934× 104 l.mol-1.cm-1 for CPL, ATL, and MTL respectively, the sensitivity index of Sand’ll were 0.0102, 0.0138, and 0.01182 µg/cm2 for CPL, ATL, and MTL respectively. LOD values for the three drugs ranged from 0.00405 to 0.00547 and LOQ values were ranged from 0.0135 to 0.0182 respectively, the method exhibits good applicability to the dosage forms and high confidence as compared with standard method and standard addition method.

GREEN PROCEDURE INDEX ASSESSMENT OF THE NOVEL STABILITY-INDICATING RP-HPLC METHOD FOR THE DETERMINATION OF CAPTOPRIL FROM PHARMACEUTICAL DOSAGE FORM

Objective: In this study, it was aimed to develop a novel reverse-phase liquid chromatography method for the ultra-sensitive determination of the antihypertensive drug captopril, using paracetamol, which is the common pain killer, as the internal standard. Optimization of all experimental conditions including composition of mobile phase, flow rate, and column temperature was carried out step by step, and the method validity of the developed method was examined according to international validation guidelines. Calibration range, linearity, the limit of determination, the limit of quantification, robustness, accuracy from commercial tablet samples, and method stability were examined in detail. In addition, the greenness profile for the developed method was assessed with the Green Analytical Procedure Index and Analytical Greenness Calculator techniques, which are frequently used in the literature. Material and Method: The chromatographic method was conducted with an XBridge C18 column (25 cm x 4.6 mm ID; 5 µm) packed with fully porous silica materials. All analyses were performed isocratically with a mobile phase containing acetonitrile:5 mM, pH 7.0 ammonium acetate solution (50:50, v/v) at a flow rate of 1.5 ml min-1. The injection volume was 5 μl, and the column was kept at 25°C in a column oven. The column eluate was monitored at 220 nm. Under optimized conditions, retention times of captopril, and paracetamol were approximately 1.59, and 2.0 min, respectively. Result and Discussion: This study described a fully validated, simple, sensitive, accurate, linear, precise, and reproducible reversed-phase liquid chromatography method for the determination of captopril in tablet samples. Under optimal experimental conditions, the linear range was found in the range of 0.5-200 µg ml-1 and the correlation coefficient was greater than 0.99. Method precision was acceptable, with coefficients of variation between 0.05% and 0.61%. In addition, as a result of the recovery studies carried out on the tablet samples, the accuracy was found to be within satisfactory limits between 99.45% and 102.55%. Moreover, the greenness profile of the developed method also showed that the method is environmentally friendly.

Identification of Bioactive Peptides from a Laminaria digitata Protein Hydrolysate Using In Silico and In Vitro Methods to Identify Angiotensin-1-Converting Enzyme (ACE-1) Inhibitory Peptides.

Bioactive peptides range in size from 2-30 amino acids and may be derived from any protein-containing biomass using hydrolysis, fermentation or high-pressure processing. Pro-peptides or cryptides result in shorter peptide sequences following digestion and may have enhanced bioactivity. Previously, we identified a protein hydrolysate generated from Laminaria digitata that inhibited ACE-1 in vitro and had an ACE-1 IC50 value of 590 µg/mL compared to an ACE-1 IC50 value of 500 µg/mL (~2.3 µM) observed for the anti-hypertensive drug Captopril©. A number of peptide sequences (130 in total) were identified using mass spectrometry from a 3 kDa permeate of this hydrolysate. Predicted bioactivities for these peptides were determined using an in silico strategy previously published by this group utilizing available databases including Expasy peptide cutter, BIOPEP and Peptide Ranker. Peptide sequences YIGNNPAKGGLF and IGNNPAKGGLF had Peptide Ranker scores of 0.81 and 0.80, respectively, and were chemically synthesized. Synthesized peptides were evaluated for ACE-1 inhibitory activity in vitro and were found to inhibit ACE-1 by 80 ± 8% and 91 ± 16%, respectively. The observed ACE-1 IC50 values for IGNNPAKGGLF and YIGNNPAKGGLF were determined as 174.4 µg/mL and 133.1 µg/mL. Both peptides produced sequences following simulated digestion with the potential to inhibit Dipeptidyl peptidase IV (DPP-IV).

Developing Metal Complexes for Captopril Quantification in Tablets Using Potentiometric and Conductometric Methods.

Potentiometric and conductometric methods were successfully applied to elucidate the interaction of 10 ions, viz., Cr3+, Fe3+, La2+, Th4+, Co2+, Mn2+, Pd2+, Sr2+, Ti2+, and Zr2+, with the antihypertensive drug captopril (CAP) and its role to determine CAP in pure powder and tablet forms. The ionization constant of CAP and the generated complexes' stability constants (log K) were evaluated using potentiometric and conductometric methods at 25 ± 0.1 °C and 0.05 M ionic strength (I) of NaNO3 aqueous solution, and CAP was then determined in pure powder and tablet forms. Complexes having metal:ligand ratios of 1:1, 1:2, and/or 1:3 were produced, regardless of the type of the ligand or metal ions. Both the suggested potentiometric and conductometric procedures were utilized to confirm the stoichiometry of the M-CAP binary complexes formed. These two different techniques were utilized successfully to determine CAP in pure powder and tablet forms. Using the standard addition method (SAM) based on the Gran plot, CAP was satisfactorily determined throughout the concentration range of 0.83-13.04 mg/mL (SD = 0.20, R = 0.9986 (n = 5)), with a detection limit of 0.64 mg/mL (SD = 0.20, R = 0.9986 (n = 5)). In the presence of common tablet excipients, no interferences were observed. The percentage of CAP recovered from various dosage formulations (tablets) varied from 95.88 to 99.92%.

POSSIBILITIES OF PROLONGED BLOOD PRESSURE MONITORING IN ASSESSMENT OF THE EFFICACY AND SAFETY OF COMBINED ANTIHYPERTENSIVE THERAPY IN EMERGENCY CARE

<b>Introduction.</b> At the stage of emergency medical care, the time of observation of a patient receiving antihypertensive therapy is limited to the time of stay of the emergency medical service team with this patient. Therefore, assessing the efficacy and safety of prescribing a particular antihypertensive treatment pattern is a relevant task. <br><b>Patients and Methods.</b> In this study, we used three two-component combinations of antihypertensive drugs (captopril and furosemide, moxonidine and furosemide, moxonidine and nifedipine) and prolonged blood pressure monitoring. We included 105 patients with a history of primary arterial hypertension who called an ambulance because of an increase in blood pressure and signed a voluntary informed consent. Evaluation of the results of prolonged blood pressure monitoring was carried out in 91 patients. The comorbidity, the clinical condition of the patient, blood pressure monitoring parameters, the efficacy and safety of antihypertensive therapy at the prehospital stage were evaluated. <br><b>Results.</b> The most pronounced and somewhat excessive hypotensive effect developed when using a combination of moxonidine with nifedipine. The index of excessive decrease in blood pressure below 120/70 mm Hg in this group was 51.6% (p<0.05), as compared to the combinations of captopril with furosemide and moxonidine with furosemide (10.3% and 7.8%, respectively). <br><b>Conclusion.</b> The use of blood pressure monitoring in patients with a clinically significant increase in blood pressure on prehospital stage allows us to assess the dynamics of blood pressure, the effectiveness and safety of prescribing various combinations of antihypertensive drugs.

H-point Standard Addition Method for the Simultaneous Spectrophotometric Determination of Captopril and Hydrochlorothiazide in Pharmaceutical Formulations

Simultaneous spectrophotometric determination of captopril and hydro-chlorothiazide in pharmaceutical formulations by the H-point standard addition method (HPSAM) is described. Absorbance at 211.5 and 230.3 nm was monitored upon the addition of standard solutions of captopril. The results showed that in prepared mixtures, captopril and hydrochlorothiazide can be determined simultaneously at concentration ratios varying from 1.0:0.8 to 2.5:1.5 μg/mL, respectively. Percentage recovery was found to be 95.33–104.37% for captopril and 96.8–105% for hydrochlorothiazide, with a relative standard deviation (RSD) of 2.46%. The method was successfully used to evaluate the antihypertensive captopril drug in a binary combination of hydrochlorothiazide in real samples with high precision and accuracy within the recovery percentage.

Interaction between Angiotensinase Activities in Pituitary and Adrenal Glands of Wistar-Kyoto and Spontaneously Hypertensive Rats under Hypotensive or Hypertensive Treatments.

In the present study, we analyzed the activity of several aminopeptidases (angiotensinases) involved in the metabolism of various angiotensin peptides, in pituitary and adrenal glands of untreated Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR) or treated with the antihypertensive drugs captopril and propranolol or with the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). Intra- and inter-gland correlations between angiotensinase activities were also calculated. Membrane-bound alanyl-, cystinyl-, and glutamyl-aminopeptidase activities were determined fluorometrically using aminoacyl-β-naphthylamide as substrates. Depending on the type of angiotensinase analyzed, the results reflect a complex picture showing substantial differences between glands, strains, and treatments. Alanyl-aminopeptidase responsible for the metabolism of Ang III to Ang IV appears to be the most active angiotensinase in both pituitary and adrenals of WKY and particularly in SHR. Independently of treatment, most positive correlations are observed in the pituitary gland of WKY whereas such positive correlations are predominant in adrenals of SHR. Negative inter-gland correlations were observed in control SHR and L-NAME treated WKY. Positive inter-gland correlations were observed in captopril-treated SHR and propranolol-treated WKY. These results may reflect additional mechanisms for increasing or decreasing systolic blood pressure in WKY or SHR.

Studi In Vitro dan In Silico EfektivitasEkstrak Mentimun (Cucumis sativus) dalam Menurunkan Hipertensi

Introduction: Hypertension is one of the major causes of stroke. Stroke can be prevented by controlling hypertension. Cucumber proved to have antihypertensive effect. cucumber contains ficetin compounds that play a role in antihypertensives. This study aims to determine the effectiveness of cucumber extract to controlling hypertension. Methods: The research method used is pre-test and post-test matched control group. The 6 wistar rats were divided into 3 groups consisting of 1 treatment groups and 2 control groups. Group P1 was induced by using ketamine 0.05 ml + epinephrine 0.2 ml + 6 ml cucumber extract, group K (-) induced by ketamine 0.05 ml + epinephrine 0.2 ml without extract, and group K (+) induced by using ketamine 0.05 ml + epinephrine 0.2 ml + captopril 2.5 mg Results The results showed that epinephrine can be used as a hypertensive inducer. cucumber extract as much as 6ml can provide antihypertensive effects. In Vitro test result showed that cucumber extract can reduce blood preassure by an average decrease in blood preassure of 102 mmHg While captopril 25,5 mmHg. Conclusions: in addition to the in vitro test, the results of the in silico test showed that the cucumber extract can significantly reduce blood pressure compared to anti-hypertensive drugs (captopril). the value of fisetin in cucumber is -9.3. and captopril only -5.7.Keywords: Hypertension, cucumber extract, In Silico, In Vitro

Enzyme-Assisted Extraction to Obtain Phenolic-Enriched Wine Lees with Enhanced Bioactivity in Hypertensive Rats.

The antihypertensive effect of the soluble fraction of wine lees (WL) from Cabernet variety grapes was recently reported by our group. This blood pressure (BP)-lowering effect was attributed to the presence of flavanols and anthocyanins. In this context, phenolic-enriched wine lees (PWL) could potentially exhibit a stronger bioactivity. Therefore, the aim of this study was to obtain a soluble fraction of WL with increased phenolic content and evaluate its functionality. The PWL were obtained using an enzyme-assisted extraction based on the hydrolysis of WL proteins with Flavourzyme®. They contained 57.20% more total phenolic compounds than WL, with anthocyanins and flavanols being the largest families present. In addition, PWL also showed greater angiotensin-converting enzyme inhibitory and antioxidant activities. Finally, the antihypertensive activity of the PWL was evaluated in spontaneously hypertensive rats. A single dose of 5 mL/kg body weight of PWL showed a greater BP-lowering effect than the one shown by WL. Moreover, this antihypertensive effect was more prolonged than the one produced by the antihypertensive drug Captopril. These results demonstrate that enzymatic protein hydrolysis is a useful method to maximize the extraction of phenolic compounds from WL and to obtain extracts with enhanced functionalities.

Small Molecule Compound Nerolidol attenuates Hypertension induced hypertrophy in spontaneously hypertensive rats through modulation of Mel-18-IGF-IIR signalling

BackgroundCardiovascular diseases are caused by multitudes of stress factors like hypertension and their outcomes are associated with high mortality and morbidity worldwide. Nerolidol, a naturally occurring sesquiterpene found in several plant species, embodies various pharmacological benefits against numerous health disorders. However, their effects on hypertension induced cardiac complications are not completely understood. PurposeThe present study is to elucidate the efficacy of nerolidol against hypertension related cardiac hypertrophy in spontaneously hypertensive rats (SHRs). Study DesignFor preliminary in vitro studies, H9c2 cardiomyoblasts cells were challenged with 200 nM Angiotensin-II (AngII) for 12 h and were then treated with nerolidol for 24 h. The hypertrophic effect in H9c2 cells were analyzed by actin staining and the modulations in hypertrophic protein markers and mediators were determined by Western blotting analysis. For in vivo experiments, sixteen week-old male Wistar Kyoto (WKY) and SHRs were segregated into five groups (n = 9): Control WKY, hypertensive SHRs, SHRs with low dose (75 mg/kg b.w/day) nerolidol, SHRs with high dose (150 mg/kg b.w/day) nerolidol and SHR rats treated with an anti-hypertensive drug captopril (50 mg/kg b.w/day). Nerolidol treatment was given orally for 8 weeks and were analysed through Echocardiography. After euthanasia, hematoxylin and eosin staining, Immunohistochemical analysis and Western blotting was performed on left ventricle tissue. ResultsWestern blotting analysis revealed that nerolidol significantly attenuates AngII induced expression of hypertrophic markers ANP and BNP in H9c2 cardiomyoblasts. In addition, actin staining further ascertained the potential of nerolidol to ameliorate AngII induced cardiac hypertrophy. Moreover, nerolidol administration suppressed the hypertrophic signalling mediators like calcineurin, GATA4, Mel-18, HSF-2 and IGFIIR in a dose-dependent fashion. In silico studies also ascertained the role of Mel-18 in the ameliorative effects of nerolidol. Further, these intriguing in vitro results were further confirmed in in vivo SHR model. Oral neraolidol in SHRs efficiently reduced blood pressure and ameliorated hypertension induced cardiac hypertrophic effects by effectively reducing the levels of proteins involved in cardiac MeL-18-HSF2-IGF-IIR signalling. ConclusionCollectively, the data reveals that the cardioprotective effect of nerolidol against hypertension induced hypertrophy involves reduction in blood pressure and regulation of the cardiac Mel-18-IGFIIR signalling cascade.

Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection.

Snake venoms, as complex mixtures of peptides and proteins, affect various vital systems of the organism. One of the main targets of the toxic components from snake venoms is the cardiovascular system. Venom proteins and peptides can act in different ways, exhibiting either cardiotoxic or cardioprotective effects. The principal classes of these compounds are cobra cardiotoxins, phospholipases A2, and natriuretic, as well as bradykinin-potentiating peptides. There is another group of proteins capable of enhancing angiogenesis, which include, e.g., vascular endothelial growth factors possessing hypotensive and cardioprotective activities. Venom proteins and peptides exhibiting cardiotropic and vasoactive effects are promising candidates for the design of new drugs capable of preventing or constricting the development of pathological processes in cardiovascular diseases, which are currently the leading cause of death worldwide. For example, a bradykinin-potentiating peptide from Bothrops jararaca snake venom was the first snake venom compound used to create the widely used antihypertensive drugs captopril and enalapril. In this paper, we review the current state of research on snake venom components affecting the cardiovascular system and analyse the mechanisms of physiological action of these toxins and the prospects for their medical application.

Study in vitro and in silico on effectiveness noni fruit extract (Morinda Citrifolia) to reducing hypertension

Hypertension is one of the major causes of stroke. Stroke can be prevented by controlling hypertension. Noni fruit proved to have antihypertensive effect. Noni Fruit contains scopoletin and xeronin compounds that play a role in antihypertensives. This study aims to determine the effectiveness of noni fruit extract to controlling hypertension. The research method used is pre-test and post-test matched control group. The 6 Wistar rats were divided into 3 groups consisting of 1 treatment group and 2 control groups. Group P1 was induced by using ketamine 0.05 ml + epinephrine 0.2 ml + 6 ml noni fruit extract, group K (-) induced by ketamine 0.05 ml + epinephrine 0.2 ml without extract, and group K (+) induced by using ketamine 0.05 ml + epinephrine 0.2 ml + captopril 2.5 mg. The results showed that epinephrine can be used as a hypertensive inducer. Noni fruit extract as much as 6ml can provide antihypertensive effects. In Vitro, test result showed that noni fruit extract can reduce blood pressure by an average decrease in blood pressure of 58,5 mmHg While captopril 25,5 mmHg. in addition to the in vitro test, the results of the in-silico test showed that the noni fruit extract can significantly reduce blood pressure compared to anti-hypertensive drugs (captopril). the value of scopoletin in noni fruit is -7.6. and captopril only -5.7.

A comprehensive study on the electrochemical advanced oxidation of antihypertensive captopril in different cells and aqueous matrices

Anodic oxidation with electrogenerated H2O2 (AO-H2O2) was applied to treat 130 mL of antihypertensive drug captopril in sulfate medium, urban wastewater and synthetic urine using a BDD, Pt or IrO2 anode and an air-diffusion cathode. Oxidants were OH formed during O2 evolution and active chlorine formed via anodic oxidation of Cl−. Drug removal decreased as: BDD > Pt > IrO2. The effect of pH and current density was examined. Further, 2.5 L of drug solutions in the same matrices with Fe2+ at pH 3.0 were treated by solar photoelectro-Fenton (SPEF) using a solar pre-pilot flow plant with a Pt/air-diffusion cell and a planar photoreactor. In sulfate medium, SPEF outperformed AO-H2O2 and electro-Fenton because of the efficient Fe3+ photoreduction. Low mineralization was achieved by the small generation of photoactive Fe(III)-carboxylate complexes. In urban wastewater, captopril was more rapidly removed due to active chlorine. Two heterocyclic derivatives and four aliphatic acids were detected.

Factors affecting in the use of antihipertension drugs with the health belief model approach in Puskesmas Pandanwangi Malang

Hypertension is a condition where systolic blood pressure is 140 mmHg or higher, and diastolic blood pressure is 90 mmHg or higher. Generally, hypertension patients use captopril and Amlodipin as treatment of hypertension. It is necessary to take various efforts to improve the obedience of hypertensive patients during drug therapy. One theory studies that obedience behavior is the Health Belief Model. The HBM theory covers perceived susceptibility, severity, benefits, and barrier, along with self-efficacy. To investigate factors affecting the obedience of hypertensive patients during the antihypertensive captopril and amlodipine medications treatment in the Puskesmas Pandanwangi, Malang, this study using the approach of HBM theory and instrument. Sampling was done through a purposive and accidental sampling method. The data analysis was done through multivariate analysis, which used multiple regression to determine the effecting factors based on the HBM theory on the obedience of hypertensive patients during the antihypertensive captopril and amlodipine medications therapy. Factors of HBM theory that affect the obedience of hypertensive patients are self-efficacy, perceived severity, and perceived barrier. Whereas, the unaffected factor are perceived suspectibility and perceived benefits. Overall, factors of HBM theory affect obedience.

Rutin as an Electrochemical Mediator in the Determination of Captopril using a Graphite Paste Electrode

AbstractA simple, rapid and sensitive cyclic voltammetry method is described for the determination of the antihypertensive drug captopril in aqueous solution using a graphite paste electrode with rutin as mediator. The catalytic role of rutin in the oxidation of captopril was confirmed by the increase observed in anodic peak current at+0.44 V vs. SCE in the presence of the mediator. Anodic peak current varied linearly with the concentration of captopril in the dynamic range 0.2 to 1.0 mmol L−1. The method exhibited a limit of detection of 89.4 μmol L−1 and a reproducibility of 1 %, values that are comparable with those exhibited by other methodologies employing electrodes without any modification. The recovery rate for the determination of captopril in a pharmaceutical sample was good (91.21 %) suggesting that the described analytical technique would be effective in industrial applications whilst offering a number of advantages over published cyclic voltammetric methods.

FAKTOR YANG BERPENGARUH TERHADAP KEPATUHAN PASIEN HIPERTENSI DALAM PENGGUNAAN OBAT ANTIHIPERTENSI DENGAN PENDEKATAN TEORI HEALTH BELIEF MODEL DI PUSKESMAS PANDANWANGI MALANG

Hypertension is a condition where systolic blood pressure is 140 mmHg or higher and diastolic blood pressure is 90 mmHg or higher. Generally, hipertensive patients uses captopril and Amlodipin as treatment of hypertension. It is necessary to take various efforts in improving the obedience of hypertensive patients during the drug therapy. One theory studies the obedience behavior is Health Belief Model. The HBM theory covers; perceived suscpetibility, perceived severity, perceived benefits, perceived barrier and self efficacy. To investigate factors effecting the obediance of hypertensive patients during the antihypertensive captopril & amlodipin medications treatment in the Local Public Health Center of Pandanwangi, Malang District using the approach of health belief model theory. This research employed MMAS-8 and HBM instrument. Sampling was done through purposive and accidental sampling method. The data analysis was done through multivariant analysis which used multiple regression to determine the effecting factors based on the HBM theory on the obedience of hypertensive patients during the antihypertensive captopril&amlodipin medications therapy. This research employed MMAS-8 and HBM instrument. Sampling was done through purposive and accidental sampling method. The data analysis was done through multivariant analysis which used multiple regression to determine the effecting factors based on the HBM theory on the obedience of hypertensive patients during the antihypertensive medications therapy. Factors of HBM Theory that affect the obedience of hypertensive patiens are; self efficacy, perceived severity, and perceived barrier. Whereas, the unaffected factor are perceived susceptibility and perceived benefits. Overall, factors of HBM theory affect the obedience. Keywords: Health belief model, obedience, captopri, amlodipin.

The role of natural products in modern drug discovery.

The global medicine market is about 1.1 trillion US dollars. About 35 percent of medicines have originated from natural products. Brazil presents the largest biodiversity in the world, with more than 50,000 species of higher plants. However, few innovative products have been developed in Brazil from active constituents derived from the Brazilian biodiversity. Scientific evidences on plants and venoms have been internationally published by Brazilian scientists over the last 4 decades; but few examples of innovative products are commercially available. Few examples include the anti-hypertensive drug captopril first identified in the venom of the Brazilian viper Bothrops jararaca by Professor Sergio Ferreira; and some phytotherapeutic agents such as Acheflan®, Syntocalmy® and Melagrião® produced by standardized plant extracts with scientific proof of safety, efficacy and quality. Still, only Acheflan® and Melagrião® are obtained from native Brazilian plants. Several issues contribute to the lack of innovative products from the Brazilian biodiversity, but in my opinion, the most challenging ones are i) the lack of specific regulations to allow researchers and companies to access biodiversity for the purposes of scientific and technological innovation; and ii) the absence of a long-term government program to support research and innovation in this field.

Neuropeptidase activity in the frontal cortex of Wistar-Kyoto and spontaneously hypertensive rats treated with vasoactive drugs: a bilateral study.

Background and objective:Hypertension can lead to mood disorders that may worsen or ameliorate depending on the type of antihypertensive prescribed. Depression is associated with modifications in basal brain asymmetry particularly that of the frontal cortex, which is involved in blood pressure control. Furthermore, different vasoactive drugs may change the brain's asymmetry in a manner that contributes to cognition status. We studied the bilateral activity of several neuropeptidases in frontal cortex as a reflect of the functional status of certain neuropeptides involved in mood.Methods:Using arylamide derivatives as substrates, we fluorometrically analysed the activity of these enzymes in the left and right frontal cortex of control untreated Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHRs) and compared their activities with WKY or SHR treated with the antihypertensive drugs captopril (CAP) and propranolol (PRO) or with the hypertensive N (G)-nitro-l-arginine methyl ester. SBP was also measured in all WKY and SHR groups.Results:Untreated WKY, WKY treated with CAP or PRO and SHR treated with CAP exhibited normotensive values of SBP. However, WKY treated with N (G)-nitro-l-arginine methyl ester as well as untreated SHR and SHR treated with PRO and N(G)-nitro-l-arginine methyl ester demonstrated hypertensive values of SBP. Changes in the bilateral distribution of neuropeptidases were depending on the strain, the enzyme analysed and the drug used. Normotensive WKY groups (WKY, CAP, PRO) revealed intrahemispheric correlations mainly in the left hemisphere. In contrast, WKY treated with N(G)-nitro-l-arginine methyl ester and SHR groups demonstrated intrahemispheric correlations mainly in the right hemisphere. Interhemispheric correlations were mostly observed in WKY as well as in SHR groups with antihypertensive treatments (CAP, PRO).Conclusion:Our results suggest specific brain bilateral patterns of neuropeptidase activities in WKY that change in SHR. This observation may be related to the cognitive disorders that have been described in these animals and that change under antihypertensive or hypertensive drug's treatments.