Antihypertensive Substances Research Articles

Bioactive peptides as antioxidants and antimicrobials: fundamentals and applications

Bioactive peptides are well-known for their remarkable tissue affinity, specificity, and effectiveness in promoting health. Extracted from food proteins, these bioactive peptides have displayed significant potential as functional foods and nutraceuticals. Throughout the years, numerous potential bioactive peptides derived from food sources have been documented. These bioactive peptides offer a wide range of crucial functions within the human body, including acting as antioxidants, antimicrobial agents, anti-inflammatory compounds, anti-hypertensive substances, and immunomodulators. More recently, extensive research has been conducted to investigate the origins, bioavailability, potential physiological effects and functionality, as well as the mechanisms of action of bioactive peptides in rendering health benefits. Researchers have also delved into various technological methods for preparing, purifying, and characterizing these peptides. This contribution primarily centers on exploring the antioxidant and antimicrobial aspects of bioactive peptides.

In Vivo Diuretic Activity and Anti-Hypertensive Potential of Hibiscus sabdariffa Extract by Inhibition of Angiotensin-Converting Enzyme and Hypertension Precursor Enzymes.

Aqueous extracts of calyx from Hibiscus sabdariffa (HS) (roselle) are highly appreciated for their nutritional and therapeutic effects, especially as anti-hypertensive substances. This study aimed to evaluate their anti-hypertensive potential through an in vitro inhibition assay of angiotensin-converting enzyme (ACE) and hypertension precursor enzymes and to assess the in vivo diuretic activity of HS. Results showed that HS extract inhibited enzymes belonging to several classes, such as α-amylase, trypsin, chymotrypsin, xanthine oxidase, lipoxygenase, and angiotensin-converting enzyme. In particular, enzymatic kinetics of ACE indicated a competitive inhibition fashion of HS extract. Furthermore, the extracts showed remarkable diuretic and natriuretic effects at doses of 50 mg/kg/bw, 100 mg/kg/b.w, and 200 mg/kg.b.w. These activities can be explained by the high content of phenolic compounds and essential amino acids. Roselle could be a potential source of nutraceuticals and anti-hypertensive bioactive compounds.

Optimasi Formulasi Tablet Lepas Lambat Ekstrak Seledri (Apium graveolens L.) Menggunakan Polimer Xanthan Gum dan Lubrikan Magnesium Stearat dengan Metode Simplex Lattice Design (SLD)

Antihypertensive drugs undergo first-pass metabolism and therefore have low oral bioavailability. It causes an increase in the frequency of drug use and concentration fluctuations that affect patient comfort. The sustained release tablet formulation was chosen because it can deliver the active substance with good bioavailability. An active antihypertensive substance that can be used is celery extract because it contains flavonoids, so a sustained release tablet formulation was made using xanthan gum and magnesium stearate to produce a constant and controlled release rate. This study aims to knowing the results of celery extract sustained release tablet evaluation using different concentrations of xanthan gum and magnesium stearate, and also obtains the optimal formulation. The manufacture of tablets uses the direct compression method. Powder evaluations include flow property through a funnel, angle of repose, compressibility index, and moisture content. Tablet evaluations include organoleptic, weight uniformity, size uniformity, hardness, friability, disintegration time, and dissolution tests. The evaluation results data were analyzed using Simplex Lattice Design. The powder evaluation result of all formulations meets the requirements of flow property through a funnel, angle of repose, compressibility index, and moisture content. Physical evaluation of the tablets shows all formulations meet the requirement of weight uniformity, hardness, and friability tests. On the size uniformity test, all formulations do not meet the requirement. The disintegration time test results show that F1 does not meet the requirement. Meanwhile, the dissolution test results show that F4 is the best formula because it shows constant and controlled release rate. Based on analyzed using Simplex Lattice Design, the F4 is the most optimal formula with xanthan gum 52 mg and magnesium stearate 3 mg.

Identification of Borassus Flabellifer Sap Compounds Against Angiotensin- Converting Enzyme for Potential Antihypertensive Inhibitors

On a global scale, cardiovascular problems have become more important recently. The existing treatments for high blood pressure are generally unsuccessful and painful for patients. Since it poses a significant risk to the cardiovascular system and the general public's health, hypertension should be carefully managed. Hypertension with a systolic reading is extremely harmful. As a result, there is increased interest in creating antihypertensive drugs with natural ingredients. The study's key finding is that Borassus flabellifer sap comprises significant bioactive components, including 9,10-Anthracenedione. The angiotensin-converting enzyme (ACE), which converts angiotensin I into the active peptide vasoconstrictor hormone angiotensin II, may be inhibited by Borassus flabellifer, according to an in-silico investigation. The 9,10-Anthracenedione and ACE molecular docking investigation revealed extremely low binding energy (-8.6 kcal/mol). One must be aware of the ACE inhibitors that are already on the market to choose an efficient ACE inhibitor. Docking interactions of 9,10-Anthracenedione hence strongly imply its potential as an antihypertensive substance. It is a possible bioactive Borassus flabellifer sap ingredient for the creation of nutraceuticals and functional foods, as well as a candidate for the development of an efficient antihypertensive medicine. According to the study's findings, Borassus flabellifer sap is a potent nutraceutical compound that can be used to treat antihypertensive.

Antihypertensive Action of Exosomes Released from the Renal Medulla after Unclipping of the Renal Artery of 2 Kidney‐1 Clip Hypertension Mice

The renal medulla has been long known to exert antihypertensive action by releasing different bioactive substances. However, so far it remains unknown what is the identity of such renal medullary antihypertensive substances. In the present study, we hypothesized that exosomes, but not a single molecule released from the renal medulla are importantly implicated in the renal medullary antihypertensive action. To test this hypothesis, we first produced the 2 kidney‐one clip (2K1C) hypertension mouse model by clipping the right renal artery (127.9 ± 1.40 mmHg vs. 94.8 ± 1.75 mmHg of sham mice). After 1 week, we unclipped the right renal artery and monitored the mean arterial blood pressure (MAP) for 1 hour and at the same time collected blood samples for analysis of exosomes. It was found that unclipping the right renal artery of 2K1C mice significanty reduced MAP by 21.2 ± 2.65 mmHg but increased the plasma exosome concentrations by more than 5 folds (before unclipping 2.9 ± 0.7 vs. 3.3±0.5, N.S., after unclipping 4±0.5 vs. 17±5× 108particles/mL, p<0.05). Immunohistochemical (IHC) assessments showed that the clipped kidneys had dramatic increase in exosome markers (CD63 and Annexin II) in the renal medulla of 2K1C mice compared to contralateral kidneys or sham mouse kidneys. These functional and IHC changes in 2K1C mice were almost completely blocked by pretreatment of mice with an exosome biogenesis inhibitor, GW‐4869 (1 mg/kg/day, i.p., n=8). We also found that rapamycin, a compound that increases autophagy and lysosome trafficking (6 mg/kg/day, i.p., n=8) substantially attenuated exosome release from the renal medulla and associated antihypertensive action in 2K1C with unclipping the right renal artery, even though it had some effects to reduce MAP and increase exosome release before the unclipping. In another series of studies using 2K1C hypertensive mice, we extracted and purified exosomes from the blood of mice with unclipping of the right renal artery and then infused these exosomes intravenously to another group of 2K1C mice. It was found that plasma exosomes from 2K1C mice with unlipping of the right renal artery signicantly reduced MAP when they are infused into recipient 2K1C mice (at a concentration of 3 x 108 exosomes) compard to exosomes from sham mice. Urinary flow and sodium excretion of recipient mice also increased slightly by infusion of exosomes from 2K1C mice. These results suggest that exosomes are enriched in the renal medulla of the clipped kidney in 2K1C mice and they can be released into the blood if the renal artery clip is released. These exosomes have strong effects to lower arterial blood pressure.

Design of telmisartan-weak acid solid dispersion to improve its solubility and stability

Telmisartan (TEL), an angiotensin II receptor antagonist, is widely used for the treatment of hypertension. However, low solubility of TEL has resulted in solubilized commercial products with alkalizers. On the contrary, our study aims to improve the solubility and dissolution rate by preparing a new TEL-solid dispersion (SD) using a weak acid. The SD formulations (SD1-0, TEL-tartaric acid-Aerosil®300 in a 1:5:3 wt ratio; SD1-6, TEL-tartaric acid-Aerosil®300: IR® in a 1:5:3:1 wt ratio) showed improved dissolution (%) by 1.19-/1.08-/1.16-fold and 1.15-/1.06-/1.11-fold compared to that of Micardis® in pH 1.2/distilled water/pH 6.8, respectively. The physical properties of the SD formulations were changed, including melting points, crystallization, and chemical interaction. Moreover, these SD formulations well maintained their stability for 12 months. In conclusion, the improved solubility and dissolution (%) of TEL in the SD formulations may result in improved bioavailability and efficacy as an anti-hypertensive substance in animals.

Management of arterial hypertension: Transfer from clinical guidelines into daily practice - Results of a survey in German practitioners offices.

INTRODUCTION:The principal objective of clinical guidelines is to improve the quality of medical care. However, standardized evaluation of the adoption into daily practice is missing. The aim of our study was to investigate the implementation of guideline recommendations on the management of arterial hypertension (AH) in German general practitioner's (GPs) offices.METHODS:A questionnaire focusing on the implementation of the German guidelines for the management of AH was developed and prospectively rolled out in 3.200 GPs and field-based specialists in internal medicine in Germany. Data were interpreted in an explorative way.RESULTS:Data from 689 German physicians that participated in the survey were analyzed. Effectiveness of lifestyle changes in the management of AH was rated as very high or high in 36.6%. When lifestyle changes only will not normalize blood pressure (BP), medical treatment will be initiated after 2–6 months by majority of physicians. Decision for mono- or combination therapy was driven by BP and patient's risk profile. Choice for a specific antihypertensive substance was based on the recommendations of scientific guidelines in the majority of GPs.CONCLUSIONS:Medication treatment algorithms recommended in 2015 by German guidelines are well accepted by GPs. Lifestyle changes are voted by only slightly more than one-third as a reasonable tool for the management of AH in the setting of the medical office. This might reflect a lack of certified medical education regarding this topic. Our study was not designed to register the time from publication of guidelines to practical implementation.

Clinical toxicology of beta-blocker overdose in adults.

Beta-blocker overdose is potentially harmful due to the strong blood pressure-lowering and heart rate-lowering effects. However, conflicting data exist as to their differential toxicity, single-substance exposures and the effect of co-exposure with additional antihypertensive medication. For this, a 10-year retrospective, explorative analysis of the Mainz Poison Center/Germany database with regard to circumstances of beta-blocker exposure, doses, symptoms and treatment was carried out. Analyses were restricted to adult patients with single-substance exposures and co-exposures with one additional antihypertensive substance. Written follow-up information was obtained in half the cases. A total of 2967 cases were analysed, of which 697 were single-substance exposures. Metoprolol was most frequently reported followed by bisoprolol, atenolol, propranolol and sotalol. Metoprolol showed a linear dose-symptom relationship, whereas propranolol and sotalol seemed to have a threshold dose beyond which symptoms aggravated. Symptoms did not differ substantially, except for more seizures being reported with propranolol, and more CNS depression/vomiting with sotalol. Activated charcoal was used in 38%, gastric lavage in 11%, temporary pacemaker in 3%, glucagon in 1%, intubation for respiratory insufficiency and cardiopulmonary resuscitation in 1% and 0.5%. All patients recovered. In 174 co-exposure cases, the distribution of poisoning severity and rate of worsening of symptoms was comparable with single-substance exposures except one patient deceased after bisoprolol and verapamil co-exposure. In adults with beta-blocker overdose, no significant differences in poisoning severity among beta-blockers were detected, and no fatalities were observed with single-substance exposures. Co-exposures with other antihypertensives, sedatives or alcohol should be carefully attended to as fatalities might occur.

Biotechnological production of the angiotensin-converting enzyme inhibitory dipeptide isoleucine-tryptophan.

Peptides with angiotensin-converting enzyme (ACE)-inhibitory and antihypertensive effects are suggested as innovative food additives to prevent or treat hypertension. Currently, these substances are isolated from food proteins following nonselective hydrolysis as a mixture of ACE-inhibitory peptides and other protein fragments. This study presents an innovative biotechnological method, based on recombinant DNA technology that was established to specifically produce the ACE-inhibitory dipeptide isoleucine-tryptophan. In a first step, a repetitive isoleucine-tryptophan construct fused to the maltose-binding protein was generated and expressed in Escherichia coli BL21 cells. The chromatographically purified recombinant fusion protein was enzymatically hydrolyzed using α-chymotrypsin to liberate the dipeptide isoleucine-tryptophan. The identity of the liberated isoleucine-tryptophan was confirmed by MS and derivatization of its N-terminus. The ACE-inhibitory effect of the recombinant dipeptide on soluble and membrane bound ACE was found to be indistinguishable from the inhibitory potential of the chemically produced commercially available dipeptide. The established experimental strategy represents a promising approach to the biotechnical production of sufficient amounts of recombinant peptide-based ACE-inhibitory and antihypertensive substances that are applicable as functional food additives to delay or even prevent hypertension.

A rapid method for the simultaneous determination of 25 anti-hypertensive compounds in dietary supplements using ultra-high-pressure liquid chromatography

ABSTRACTA novel, stable, simple and specific ultra-performance liquid chromatography method with ultraviolet detection (205 nm) for the simultaneous analysis of 25 anti-hypertensive substances was developed. The method was validated according to the International Conference of Harmonisation guidelines with respect to linearity, accuracy, precision, limit of detection (LOD), limit of quantitation (LOQ) and stability. From the ultra-performance liquid chromatography results, we identified the LOD and LOQ of solid samples to be 0.20–1.00 and 0.60–3.00 μg ml−1, respectively, while those of liquid samples were 0.30–1.20 and 0.90–3.60 μg ml−1, respectively. The linearity exceeded 0.9999, and the intra- and inter-day precisions were 0.15–6.48% and 0.28–8.67%, respectively. The intra- and inter-day accuracies were 82.25–111.42% and 80.70–115.64%, respectively, and the stability was lower than 12.9% (relative standard deviation). This method was applied to the monitoring of 97 commercially available dietary supplements obtained in Korea, such as pills, soft capsules, hard capsules, liquids, powders and tablets. The proposed method is accurate, precise and of high quality, and can be used for the routine, reproducible analysis and control of 25 anti-hypertensive substances in various dietary supplements. The work presented herein may help to prevent incidents related to food adulteration and restrict the illegal food market.

Awareness, treatment, and control of hypertension in Austria: a multicentre cross-sectional study.

Hypertension (HTN) control is achieved in 30-50% of all diagnosed and treated patients in Europe today. There is no large, recent, and properly conducted Austrian study available, with the last representative data being obtained in the 1990s. We sought to close this gap of evidence in Europe by providing information on HTN control in predominantly adherent patients. In October 2015, we enrolled 4303 patients with HTN who approached one of 158 participating pharmacies with a prescription filled for antihypertensive medication. The recruitment was completed within 10 days. Patient's mean age was 68 ± 12 years, 53% were women. The mean SBP/DBP was 144 ± 20/84 ± 12 mmHg. On average, patients received 2.2 ± 1.1 different antihypertensive substances, 45% received a fixed-dose combination drug. A total of 93% were aware of their disease, 90% claimed to have taken their medication prior to the survey, and 41% had their blood pressure (BP) controlled at a threshold of 140/90 mmHg. Predictors of HTN control were lower age [per decade increase, odds ratio (OR) 0.90, 95% confidence interval (CI) 0.85; 0.96, P < 0.01], female sex (OR 1.23, 95% CI 1.07;1.41), the intake of medication on the day of the conduct of the survey (OR 2.15, 95% CI 1.67;2.76), a university degree (OR 1.58, 95% CI 1.19; 2.08), and the consultation of a specialist for internal medicine/cardiology vs. a general practitioner (OR 1.20, 95% CI 1.04; 1.39). Despite a high degree of awareness and frequent use of fixed-dose combination drugs, only 41% of diagnosed, treated, and adherent HTN patients had their BP controlled. Immediate action is required to improve BP control in Austria. : http://links.lww.com/HJH/A624.

Preparation of Biological Samples Containing Metoprolol and Bisoprolol for Applying Methods for Quantitative Analysis

Abstract Arterial hypertension is a complex disease with many serious complications, representing a leading cause of mortality. Selective beta-blockers such as metoprolol and bisoprolol are frequently used in the management of hypertension. Numerous analytical methods have been developed for the determination of these substances in biological fluids, such as liquid chromatography coupled with mass spectrometry, gas chromatography coupled with mass spectrometry, high performance liquid chromatography. Due to the complex composition of biological fluids a biological sample pre-treatment before the use of the method for quantitative determination is required in order to remove proteins and potential interferences. The most commonly used methods for processing biological samples containing metoprolol and bisoprolol were identified through a thorough literature search using PubMed, ScienceDirect, and Willey Journals databases. Articles published between years 2005-2015 were reviewed. Protein precipitation, liquid-liquid extraction and solid phase extraction are the main techniques for the extraction of these drugs from plasma, serum, whole blood and urine samples. In addition, numerous other techniques have been developed for the preparation of biological samples, such as dispersive liquid-liquid microextraction, carrier-mediated liquid phase microextraction, hollow fiber-protected liquid phase microextraction, on-line molecularly imprinted solid phase extraction. The analysis of metoprolol and bisoprolol in human plasma, urine and other biological fluids provides important information in clinical and toxicological trials, thus requiring the application of appropriate extraction techniques for the detection of these antihypertensive substances at nanogram and picogram levels.

REGINOAL PECULARITIES OF HYPOTENSIVE DRUGS USE BY PREGNANT WOMEN

Hypotensive drugs applied by pregnant women in gestational and post-gravidary periods are limited by four basic groups of antihypertensive substances. Administration of other drugs is rare and do not have a tendency to grow. The majority of drugs corresponds to the following criteria: they are low cost, they are used during several decades. Beta-adrenergic blockers are the leaders among the hypotensive drugs for pregnant women. On the whole, pharmacotherapy of a high blood pressure of contingent under study corresponds to international recommendations

Treatment of Hypertensive Patients with a Fixed-Dose Combination of Bisoprolol and Amlodipine: Results of a Cohort study with More Than 10,000 Patients.

IntroductionMany patients need more than one antihypertensive agent for effective blood pressure (BP) control. Prescription of a fixed-dose combination (FDC) of bisoprolol and amlodipine in one tablet has been shown to significantly improve patient adherence. This non-interventional study investigated the effects on adherence and BP control of switching from a free-dose combination of the two antihypertensive substances to a FDC in a larger patient population.MethodsPatients aged ≥18 years with essential hypertension were switched at least 4 weeks prior to study initiation from a free-dose combination of bisoprolol and amlodipine to the FDC. Dosage adjustment was implemented only if medically indicated. Adherence was assessed on the basis of the ratio of pills used to pills dispensed (%) at each visit (pill count). BP and key laboratory values were determined at baseline, 3 and 6 months.Results10,532 patients (average age 59 years; 48% female) were recruited between 2013 and 2014; 22% of patients had type 2 diabetes and 38% had cardiovascular disease. The mean doses of the freely combined drugs prior to switching were 5.5 mg bisoprolol and 6.1 mg amlodipine once daily. The mean daily doses prescribed in the FDC were 5.8 and 6.4 mg, respectively. Pill counts at 6 months revealed a good to excellent adherence in >95% of the patients. Comparison of BP at baseline and at 6 months showed substantial changes (mean systolic BP: 147.3 vs. 130.9 mmHg; mean diastolic BP: 87.9 vs. 79.1 mmHg). Clinically relevant improvement in systolic BP was established for 82% of patients. In patients with comorbidities, switching to FDC produced a substantial improvement in BP. A total of 89 (0.7%) adverse events (AEs) were reported, including edema, headache, dizziness, bradycardia, nausea, and skin reactions. Only three AEs were classified as serious.ConclusionThese data from a non-interventional study in a large patient population demonstrate the benefits of prescribing a FDC of bisoprolol–amlodipine in terms of an excellent adherence and an associated improvement in control of previously elevated BP, which may be relevant in real-life practice.FundingMerck KGaA.Electronic supplementary materialThe online version of this article (doi:10.1007/s40119-015-0045-z) contains supplementary material, which is available to authorized users.

Edible Filamentous Fungi from the Species Monascus: Early Traditional Fermentations, Modern Molecular Biology, and Future Genomics

AbstractMonascus spp. are filamentous fungi famous for their fermented products, especially red mold rice (RMR), a traditional fermented food in East Asian areas with a very long edible history documented back to the Han dynasty (BC 202‐AD 220) in China. Nowadays, RMR and its related products involve a very large industry from artisanal traditional fermentations to food companies to medicine manufacturers, which are distributed worldwide. Modern studies have shown that Monascus spp. are able to produce abundant beneficial secondary metabolites, such as monacolins (cholesterol‐lowering agents), γ‐amino butyric acid (an antihypertensive substance), dimerumic acid (an antioxidant), and pigments (food‐grade colorants), and some strains can also secrete citrinin, a nephrotoxic metabolite. Monascus‐related studies have received much attention because of their wide applications. However, to our knowledge, no systematic review on the progress of Monascus research has ever been published. In this review, the progress of research on Monascus is summarized into 3 stages: Monascus fermentation, Monascus molecular biology, and Monascus genomics. This review covers the past history, current status, and future direction of Monascus research, contributing to a comprehensive understanding of Monascus research progress.

Enhanced levels of nicotianamine promote iron accumulation and tolerance to calcareous soil in soybean.

Iron (Fe) is an essential nutrient in both plants and humans. Fe deficiency on calcareous soil with low Fe availability is a major agricultural problem. Nicotianamine (NA) is one of the Fe chelator in plants, which is involved in metal translocation into seeds, and serves as an antihypertensive substance in humans. In this study, soybean plants overexpressing the barley NA synthase 1 (HvNAS1) gene driven by the constitutive CaMV 35S promoter were produced using Agrobacterium-mediated transformation. The transgenic soybean showed no growth defect and grew normally. The NA content of transgenic soybean seeds was up to four-fold greater than that of non-transgenic (NT) soybean seeds. The level of HvNAS1 expression was positively correlated with the amount of NA, and a high concentration of NA was maintained in the seeds in succeeding generations. The Fe concentration was approximately two-fold greater in transgenic soybean seeds than in NT soybean seeds. Furthermore, the transgenic soybeans showed tolerance to low Fe availability in calcareous soil. Our results suggested that increasing the NA content in soybean seeds by the overexpression of HvNAS1 offers potential benefits for both human health and agricultural productivity.

In vitro ACE-inhibitory activity and in vivo antihypertensive effects of water-soluble extract by Parmigiano Reggiano and Grana Padano cheeses

Angiotensin converting enzyme (ACE)-inhibitory activity and the anti-hypertensive effect of naturally formed bioactive peptides in a lyophilised water-soluble extract (WSE) from 32-month-aged Parmigiano Reggiano (PR) and Grana Padano (GP) cheeses were assessed. ACE-inhibitory activity was evaluated on undigested and in vitro digested WSE: consistent ACE-inhibitory activity in both hard cheeses was found. Twenty spontaneously hypertensive rats were used to test the hypotensive action of lyophilised WSEs from PR and GP cheeses; systolic (SBP) and diastolic (DBP) blood pressures were recorded by a non-invasive tail-cuff method. In vivo administration of GP and PR WSE did not induce a reduction of SBP and DBP after ten weeks of treatment. These results clearly indicate that in vitro ACE-inhibitory activity cannot be used as an exclusive criterion to evaluate potential anti-hypertensive substances. Therefore, in vivo testing of the anti-hypertensive effects of bioactive peptides is necessary to confirm beneficial effects.

Vasorelaxing and Antihypertensive Effects of 7,8-Dihydroxyflavone

Although 7,8-dihydroxyflavone (7,8-DHF) has been demonstrated to be potently neuroprotective, its effect on vascular function remains unknown. The effect of 7,8-DHF on phenylephrine (PE)-induced preconstriction was examined with aortic rings isolated from normal rats. Its effective mechanisms were studied with blockers, Western blotting, and primarily cultured vascular smooth myocytes. The blood pressure (BP) of rats was measured with a tail cuff method. 7,8-DHF dose-dependently dilated the PE-preconstricted, endothelia-intact aortic rings with concentration for 50% of maximal effect (EC50) of approximately 24 µM. Both Nω-nitro-L-arginine methyl ester hydrochloride, a nitric oxide synthase inhibitor, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a soluble guanylyl cyclase blocker, significantly reduced the vasorelaxing effect of 7,8-DHF. Western blotting showed that 7,8-DHF increased the aortic endothelial nitric oxide synthase protein expression and phosphorylation. With endothelia removed, 7,8-DHF also dilated the PE-preconstricted rings but with EC50 of approximately 104 µM. Ca(2+) imaging experiments detected that 7,8-DHF probably blocked both intracellular Ca(2+) release and extracellular Ca(2+) influx. Therefore, the mechanisms of 7,8-DHF dilating effect might be stimulating the nitric oxide/cGMP production and blocking the Ca(2+) signaling pathway instead of tropomyosin receptor kinase B receptors because ANA-12, its specific antagonist, did not show any effect against 7,8-DHF. When administered intravenously, 7,8-DHF significantly reduced the BP of the spontaneously hypertensive rats. However, when used orally, there was only a slight but significant reduction in the diastolic pressure. The results suggest that neuro-protective 7,8-DHF is also a vasorelaxing and antihypertensive substance in rats.

Prevalence and determinants of controlled hypertension in a German population cohort

BackgroundData of the German population-based cohort SHIP (Study of Health in Pomerania) were analysed to examine treatment rates, antihypertensive substances prescribed, and the proportion of hypertensive study participants reaching target values for blood pressure as well as determinants.MethodsThe study population was defined using baseline data of the cohort (collected between 1997 and 2001). Participants with blood pressure values ≥140/90 mmHg and/or antihypertensive medication with known hypertension and participants with risk-comorbidity (diabetes, stroke, angina pectoris, and/or myocardial infarction) and blood pressure values ≥130/80 mmHg were included. The analysis of treatment and target values was based on the 5-year follow-up of the cohort (collected between 2002 and 2006). Logistic regression was used to identify determinants for a normotensive blood pressure.Results3278 SHIP-participants with hypertensive blood pressure values were included (mean age: 55.5 years; SD 13.6, range 21–80 years). The raw hypertension prevalence was 50.9% (N = 1761). 58.7% (N = 1074) of all hypertensive patients reported some form of antihypertensive treatment. Thereof 65.1% (N = 728) received combination therapy. Of the patients without risk-comorbidity, 42.1% (N = 489) reached their target blood pressure values at the time of the 5-year follow-up of the cohort. Of the patients with any risk-comorbidity this proportion was only 21.7% (N = 131). Significant determinants for reaching the target values were being female and having antihypertensive combination therapy. Increasing age, having risk-comorbidities, and obesity were negatively associated with reaching the target values.ConclusionsBoth the proportion of participants receiving therapy and the number of participants reaching their target blood pressure values are very low. Combination therapy is associated with better blood pressure control as compared to mono therapy. However, even in the subgroup of hypertensive patients under combination therapy only 36% (both patients with and without comorbidity) reach target values.

Renal Denervation Therapy: Indications and Success Factors

Arterial hypertension is a common and an increasing health care problem. In Germany and other Western countries, prevalence rates are as high as 50%. Of these, 13% of patients suffer from refractory hypertension, where the target blood pressure is not achievable with &gt;3 antihypertensive substances. Renal denervation therapy (RDT) is a relatively new, catheterization-based intervention to treat patients with refractory hypertension. The rationale of RDT is the mechanical destruction with high frequency ablation of renal sympathetic fibers, which can be easily accessed via the renal artery. The first clinical trials evaluating effect and safety of the procedure have been promising, and RDT is being routinely used in specialized centers.