INTRODUÇÃO: A hipertensão renovascular (HRV) decorrente da estenose de artéria renal (EAR) é uma patologia potencialmente curável, mas os benefícios da revascularização não são alcançados por todos porque selecionar pacientes com base nos critérios clínicos ou angiográficos pode não ser suficiente para se obter o sucesso clínico. Existe um grande interesse em se desenvolver exames para detectar a presença de EAR e avaliar seu significado funcional. OBJETIVOS: avaliar se a redução da Taxa de Filtração Glomerular (TFG) medida com EDTA-51Cr após o uso de captopril consegue diferenciar pacientes hipertensos com EAR daqueles sem estenose da artéria e avaliar se existe correlação entre as variações da TFG e a evolução de pacientes submetidos a diferentes tratamentos. MÉTODOS: Foram estudados 41 pacientes com hipertensão arterial de difícil controle que foram divididos em dois grupos: GP: 21 pacientes com EAR e GH: 20 pacientes sem EAR. Os pacientes foram submetidos à medida de TFG com EDTA-51Cr pré e após a administração do captopril. Os pacientes do GP realizaram simultaneamente cintilografia com DMSA-99mTc para avaliação da função renal diferencial. Os pacientes com estenose de artéria renal foram subdivididos de acordo com o tratamento recebido: clínico (GP-CL) ou por intervenção (GP-I). As medidas das TFGs antes e após o captopril foram comparadas entre os grupos. Foi também, investigado se a relação pré/pós captopril tinha correlação com a resposta clínica dos pacientes. RESULTADOS: a média da TFG (ml/min./1,73m2) no total de pacientes estudados, foi de 56,7±26,5 na fase pré-captopril e 47,0±24,4 após o captopril. A modificação da TFG determinada pelo captopril,foi avaliada pela relação da filtração glomerular pré/pós-captopril. A média da relação TFG pré/pós-captopril foi 1,36 ±0,54 no grupo total de pacientes e quando foi feita a comparação entre a TFG pré e pós-captopril, houve uma redução significativa (p= 0,016). O GH mostrou relação média da TFG pré/pós-captopril de 1,13, valor significativamente menor que o GP que teve a relação média de 1,57 (p= 0,007). Quando foi avaliada a variação da TFG após o captopril nos dois grupos não foi observada diferença estatisticamente significativa no GH (p=0,68), mas observou-se diferença significativa no GP (p<0,001). No total, 15 pacientes apresentaram melhora dos seus níveis pressóricos, sendo oito do grupo de intervenção e sete do grupo clinico, não havendo diferença estatisticamente significativa em relação à melhora clínica entre os dois grupos (p=0,36). Quando comparamos os pacientes com e sem melhora clínica não se observou diferença significativa na TFG basal (p=0,09) ou na relação TFG pré/pós-captopril (p=0,74). A função renal diferencial obtida pelo DMSA-99mTc pré e pós captopril não mostrou diferença estatisticamente significativa nos rins com e sem estenose, (p=0.09). CONCLUSÃO: O captopril acarreta uma redução significativa da TFG e esta redução é mais acentuada em pacientes com EAR, mas não houve correlação entre as mediadas da TFG e a evolução clínica dos pacientes / INTRODUCTION: Renovascular hypertension (RVH) resulting from renal artery stenosis (RAS) is a potential curable pathology, but the revascularization benefits are not reached among all patients because selecting patients on the basis of clinical and angiographic criteria may not be sufficient to achieve clinical success. There has been increasing interest in developing screening tests capable of accurately detecting the presence of RAS and also of evaluating its functional consequences PURPOSE: the purpose of this study was to evaluate if captopril induced changes in 51Cr-EDTA clearance could be used to differentiate between hypertensive patients with and without renal artery stenosis and to investigate if there was a correlation between these changes and patients clinical response to therapy. METHODS: 41 patients with poor-controlled severe hypertension were studied. Patients were divided into two groups: GP=patients with renal artery stenosis (n=21), and GH=patients without renal artery stenosis (n=20). They were submitted to a Glomerular Filtration Rate (GFR) measurement with EDTA-51Cr pre and post captopril administration. The GP patients were submitted simultaneously to 99mTc-DMSA scintigraphies to estimate individual renal function. GP patients were further subdivided according to the treatment strategy: optimization of clinical treatment (GP-Cl) and interventional procedures (GP-I). The GFRs before and after captopril administration were compared between the groups. It was also investigated if baseline to post-captopril GFR ratio had a correlation to clinical response of patients. RESULTS: The GFR average (ml/min./1,73m2) on the total patients, was 56,7±26,5 on pre-captopril phase and 47,0±24,4 post captopril. The GFR alteration determinated by captopril was evaluated by Baseline/post-captopril GFR ratio. Baseline/post-captopril GFR mean ratio was 1,36 in total patients and the GFR had a significant decrease after captopril administration (p value 0.016). Baseline/post-captopril GFR mean ratio in GH was 1.13, value significantly lower than the GP which had the average relation of 1,57 (p= 0,007). When GFR pre and post-captopril was compared among the two groups separately, there was no significantly difference on the GH (p=0,68), but a expressive difference was observed on GP (p<0,001). 15 patients had a clinical response to the treatment. Clinical response was observed in 8/10 patients from GP-I and 7/11 from GP-Cl and there was not observed a significantly difference between the two groups (p=0,36). Comparing the groups with or without clinical improvement there was not a significantly difference on the GRF baseline (p=0,09) or on or baseline/post-captopril ratio (p=0,74). When evaluating the differential renal function obtained by pre and post-captopril DMSA-99mTc, significantly difference was not observed (p=0.09) for the kidneys with or without stenosis. CONCLUSION: captopril induced a decrease in GFR of hypertensive patients and it is more pronounced in patients with renal artery stenosis, but no correlation was observed between captopril induced decrease in GFR and clinical response of patients submitted to interventional or clinical treatment

The rapid development, approval, and production of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than 1 year after the first reports of a new infectious disease was a real game changer, providing 80%–90% efficacy in preventing severe etiopathologies of the coronavirus disease 2019 (COVID-19). These vaccines induce an immune response against the SARS-CoV-2 spike (S) protein located on the surface of the virus particle. Antibodies (Abs) recognizing the S-protein can inhibit binding of the virus via the S-protein to the angiotensin-converting enzyme-2 (ACE-2) receptor expressed on different human cells, especially when these Abs bind to the interaction site, the so-called receptor-binding domain (RBD). We have expressed the RBDs of wild-type SARS-CoV-2 and five variants of concern (VOCs) to test the immune response in people before vaccination with mRNA vaccines BNT162b2 and mRNA-1273 and after up to three vaccinations using in-house ELISA and inhibition assays. The methods of both assays are provided. Both vaccines initiated similarly high IgG titers after two vaccinations against the wild-type and even two VOC-RBDs (alpha and delta) and strongly inhibited the corresponding RBD-ACE-2 binding. The IgG titers and inhibition of ACE-2 binding were lower for beta and gamma RBDs and much lower for omicron RBD. The third vaccination after 6 months strongly increased both the IgG titers and the neutralizing effect against all variants, especially for omicron, leading to 63% ± 13% neutralization potential. Importantly, neutralization linearly increased with the IgG titers.

No description available.

Coronary artery disease (CAD) is the leading cause of mortality worldwide and atrial fibrillation (AF) is a prevalent arrhythmia associated with increased risk of mortality and morbidity. Despite improved outcome in both diseases, there is a need to further describe the prevalence, outcome and management of CAD in patients with concomitant AF. AF was a common finding among patients with MI, with 16% having new-onset, paroxysmal or chronic AF. Patients post-MI with concomitant AF, regardless of subtype, were at increased risk of composite cardiovascular outcome of mortality, MI or ischemic stroke, including mortality and ischemic stroke alone. No major difference in outcome was observed between AF subtypes. At discharge, an oral anticoagulant was prescribed to 27% of the patients with MI and AF undergoing percutaneous coronary intervention (PCI). Aspirin or clopidogrel plus warfarin versus dual antiplatelet therapy with aspirin plus clopidogrel were associated with similar 0-90-day and lower 91-365-day risk of cardiovascular outcome, without increased risk of major bleeding events. Triple therapy with aspirin, clopidogrel plus warfarin versus dual antiplatelet therapy was associated with non-significant lower risk of cardiovascular outcome, but with increased risk of bleeding events. Treatment with renin-angiotensin system (RAS) inhibitors post-MI was associated with lower risk of all-cause and cardiovascular mortality in patients with and without congestive heart failure and/or AF. However, RAS inhibition in patients without AF was not associated with lower risk of new-onset AF. Approximately 1 in 3 patients undergoing isolated coronary artery bypass grafting (CABG) had pre- or postoperative AF. Patients with AF, regardless of subtype, were at higher risk of all-cause mortality, cardiovascular mortality and congestive heart failure. Furthermore, postoperative AF was associated with higher risk of recurrent AF. In conclusion, AF was a common finding in the setting of MI and CABG. AF, irrespectively if in the setting of MI or CABG was associated with higher risk of ischemic events and mortality. Also, postoperative AF was associated with recurrent AF. Oral anticoagulants post-MI and PCI in patients with AF was underutilized, however, optimal antithrombotic therapy is still unknown. RAS inhibition post-MI seems beneficial, however, it was not associated with lower incidence of new-onset AF.

Stroke is a common, multifactorial cardiovascular disease. A stroke event is the result of traditional risk factors (i.e. hypertension, diabetes, smoking), environmental exposures and genetic factors in a complex interplay. The genetic contribution is, as estimated by studies on the influence of family history on the risk of stroke, limited on the individual level, and overridden by, for example the excess risk associated with smoking. On the population level, and as a means to better understand the etiology of stroke, genetics can play a major role. Northern Sweden is well suited for studying the genetic aspects of stroke. The population shows signs of founder effects, and is relatively homogeneous. Large-scale cardiovascular health surveys, the MONICA Project and the Västerbotten Intervention Program, allow studies on risk factors in relation to stroke. Two prospective nested case-referent study samples, (113 cases and 226 controls; 275 cases and 549 controls), and a set of 56 families (117 affected) were collected for functional candidate gene association, and linkage, studies. The selected candidate genes included haemostatic factors and genes within the renin angiotensin system (RAS). Functional single nucleotide polymorphisms (SNPs) that influence the levels of PAI-1 (PAI-1 4G/5G), and tPA (tPA -7,351C&gt;T), have been identified. The angiotensin converting enzyme insertion/deletion polymorphism (ACE I/D) has been shown to be associated with ischaemic stroke. The angiotensin II receptor type 1 A1166C polymorphism (AT1R A1166C), less extensively studied, has been suggested to be associated with stroke, and to interact with the ACE I/D. We found that the PAI-1 4G/4G genotype was associated with an increased risk of future ischaemic stroke (OR 1.79, 95%CI 1.01-3.19), and this was replicated in a second study sample. Furthermore, levels of serum triglycerides modulated the effect of the genotype. In the study on tPA, no association between the tPA -7,351C&gt;T polymorphism and the risk of stroke was found in an analysis of the two study samples pooled. The two RAS polymorphisms were prospectively associated with ischaemic stroke independently of each other and other risk factors (OR 1.60, p=0.02 and OR 1.60, p=0.04, respectively). A candidate region linkage study, focusing on a previously reported stroke susceptibility locus on chromosome 5, was performed in a set of families. In addition, association between ischemic stroke and the positional candidate gene phosphodiesterase 4D (PDE4D) was tested. Linkage to 5q12 was replicated in this independent population, but not PDE4D association with stroke. This suggests that alternative genotypes in this stroke susceptibility locus contribute in different populations. In conclusion, the genetic component in the causation of stroke was investigated. The results of the functional candidate gene association studies showed (1) interaction between PAI-1 genotype and a putatively modifiable risk factor, triglycerides, (2) a prospective testing of the tPA SNP with no association detected, and (3) a novel, hypothesis-generating, finding in the case of AT1R polymorphism and the risk of ischaemic stroke. The replication of linkage to chromosome 5q12 in our northern Swedish population was interesting, and it will be further explored.

As doenças cardiovasculares (DCV) são responsáveis pela maioria das mortes ocorridas em todo o mundo. Os riscos para o desenvolvimento destas patologias podem ser amenizados, em parte, por meio de uma dieta rica em alimentos de origem vegetal. Neste sentido, os frutos nativos brasileiros, como os pertencentes à família Myrtaceae, podem contribuir para melhorar a qualidade da alimentação, pois apresentam altos teores de compostos bioativos, entre eles, os fenólicos (CBF). Pouco se sabe sobre os efeitos dos polifenóis destes frutos para redução do risco de desenvolvimento das DCV. Sendo assim, este trabalho buscou avaliar a bioacessibilidade dos CBF presentes em polpas de cambuci e jabuticaba e seus efeitos in vitro sobre mecanismos de ação relacionados às DCV. Para tanto, extratos ricos em polifenóis foram obtidos a partir de extrações em fase sólida (C18 e PA) das polpas de ambos os frutos, submetidas ou não à simulação da digestão gastrointestinal. Estes extratos tiveram seus efeitos inibitórios sobre a atividade da Enzima Conversora de Angiotensina I (ECA) e a agregação plaquetária induzida por adenosina difosfato avaliados in vitro. De acordo com os resultados obtidos, a digestão in vitro foi capaz de liberar os CBF da matriz alimentar. Tal bioacessibilidade parece ter sido importante apenas para a inibição da agregação plaquetária, uma vez que a capacidade inibitória destes compostos sobre a atividade da ECA não melhorou depois da digestão in vitro. Quanto aos resultados obtidos pelos extratos provenientes das colunas PA e C18, observa-se que as maiores concentrações de taninos nestes últimos não foram suficientes para melhorar a capacidade antiagregante, mas foram importantes para aumentar a inibição da atividade da ECA. Comparando-se as respostas apresentadas pelos dois frutos, os CBF presentes no cambuci exibiram, predominantemente, potenciais anti-hipertensivo e antiagregantedo maiores do que os da jabuticaba. Neste contexto, o consumo de cambuci e jabuticaba, bem como a utilização de seus polifenóis purificados, podem ser adjuvantes para a redução dos riscos relacionados ao desenvolvimento das DCV. / The cardiovascular diseases (CVD) are the leading cause of death worldwide. The risk of development of these disorders can be reduced, partially, by a vegetal-based diet. In this way, the Brazilian native fruits from Myrtaceae family may contribute to improve the diet quality, once they have high quantity of bioactive compounds, such as the phenolic (PC). The knowledge about the cardioprotective effects of consuming these fruit polyphenols is limited, so this study aimed to evaluate the bioaccessibility of the cambuci and jaboticaba PC and their in vitro potential on CVD-related mechanisms. First, gastrointestinal digestion simulation of each fruit pulp was done, and then the polyphenols rich extracts were obtained by solid phase extractions, before and after the pulps digestion. The polyphenols rich extracts had their phenolic concentrations determined and were used to evaluate the capacity of PC in inhibit the Angiotensin Converting Enzyme (ACE) activity and the platelet aggregation induced by ADP. The results were expressed as IC50, considering the total phenolic content per milliliter of reaction. According to the results, the in vitro digestion process was able to release the polyphenols from the food matrix. Therefore, the bioaccessibility had no significant effect on ACE activity, but decreased the IC50 values of platelet aggregation. In relation to the extracts from PA and C18 columns, the higher tannin concentration In comparison to the IC50 values presented by PA extracts, the higher concentrations of tannins in the last one were not enough to improve the antiaggregant effect, but were important to increase the inhibition of ACE activity. Cambuci polyphenols presented higher antihypertensive and antiaggregant potentials than the jaboticaba compounds. In this respect, the ingestion of cambuci and jaboticaba and the use of their purified polyphenols can be of particular importance in reducing the risk for the CVD development.

Na África subsaariana, as serpentes do gênero Bitis são de extrema importância, pois suas vítimas apresentam sintomas como dano local, hemorragia e uma severa hipotensão. Este trabalho identificou moléculas capazes de inibir a atividade da enzima conversora de angiotensina I (ECA) presentes no veneno de quatro serpentes do gênero Bitis. Para isto, as porções de baixa massa molecular desses 4 venenos foram fracionadas em RP-HPLC e as frações com boa inibição sobre a atividade da ECA foram analisadas por espectrometria de massas. Foram identificados 34 oligopeptídeos ricos em prolina (PRO), sendo 8 sintetizados e suas constantes de inibição (Ki) determinadas. Em testes com substratos naturais da ECA, angiotensina I e bradicinina, foi constatada a maior inibição da hidrólise da angiotensina I por quatro PROs. Todos os PROs in vivo reduziram a pressão arterial, e seis deles aumentaram a frequência cardíaca em ratos Wistar. Com isto, conclui-se que existem toxinas no veneno de serpentes do gênero Bitis responsáveis pela hipotensão. / In the sub-saharian Africa, snakes from the Bitis genus are of extreme medical importance, since its victims show symptoms as local tissue damage, hemorrhage and a severe hypotension. This work identified molecules that inhibit the angiotensin I converting enzyme (ACE) in the venom of 4 snakes from the Bitis genus. The low molecular portions of the venom of these snakes were fractionated in RP-HPLC and the fractions that efficiently inhibited the ACE activity were analyzed by mass spectrometry. 34 proline-rich oligopeptides were identified, 8 of them synthesized and had their inhibition constants (Ki) determined. In tests using natural substrates of ACE, angiotensin I and bradykinin, the angiotensin I hydrolysis were better inhibited by four PROs. In vivo tests results showed that all PROs decreased the mean arterial pressure and six of them increased the heart rate. Therefore, we can conclude that there are toxins present in the venom of Bitis capable of cause hypotension.

<p>Tulbaghia violacea Harv. (Alliaceae) is a small bulbous herb which belongs to the family, Alliaceae, most commonly associated with onions and garlic. In South Africa (SA), this&nbsp / herb has been traditionally used in the treatment of various ailments, including fever, colds, asthma, paralysis, hypertension (HTN) and stomach problems. The aim of this study&nbsp / was to evaluate the effect of methanol leaf extracts (MLE) of T. violacea on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats / &nbsp / and to find out the mechanism(s) by which it acts. The MLE of T. violacea (5 - 150 mg/kg), angiotensin I (ang I, 3.1 - 100 &mu / g/kg), captopril (10 mg/kg), angiotensin II (ang II, 3.1 - 50&nbsp / g/kg), losartan (30 mg/kg), phenylephrine (0.01 &ndash / 0.16 mg/kg), prazosin (1 mg/kg), dobutamine (0.2 &ndash / 10.0 &mu / g/kg), propranolol (0.1 - 12.8 mg/kg), muscarine (0.16 -10 &mu / g/kg),&nbsp / and atropine (0.02 - 20.48 mg/kg) were administered intravenously into male spontaneously hypertensive rats (SHR) weighing between 300 g and 350 g and aged less than 5&nbsp / months. The MLE of T. violacea and/or the standard drugs were infused alone, simultaneously, or separately into each animal. The BP and HR were measured via a pressure&nbsp / transducer connecting the femoral artery and the Powerlab. The vehicle (0.2 mls of a mixture of dimethylsulfoxide and normal saline), T. violacea (60 mg/kg) and captopril (10&nbsp / mg/kg) were injected intraperitoneally into some SHR for 21 days to investigate the chronic effect of these agents on plasma levels of aldosterone. The mean change, the mean&nbsp / of the individual percentage changes and the percentage difference (in mean) observed with each intervention was calculated and statistically analyzed using the Student&rsquo / s t test&nbsp / for significant difference (p &lt / 0.05). The Microsoft Excel software was used for statistical analysis. T. violacea significantly (p &lt / 0.05) reduced the systolic, diastolic, and mean&nbsp / arterial BP / and HR dose-dependently. In a dose-dependent manner, ang I, ang II, phenylephrine significantly (p &lt / 0.05) increased the BP, while propranolol, muscarine and&nbsp / atropine reduced the BP. The increases in BP due to dobutamine were not dose-dependent. In a dose dependent manner, phenylephrine and propranolol reduced the HR, while dobutamine increased the HR. The effect of ang I, ang II, muscarine and atropine on HR were not dose-dependent / with both increases as well as decreases observed with ang&nbsp / I, and II and atropine, while decreases were seen with muscarine. Captopril produced&nbsp / significant (p &lt / 0.05) reduction in BP which were not associated with any change in HR. The co-infusion of ang I with the MLE produced significant (p &lt / 0.05) reduction in BP, which were not associated with significant changes in HR. The co-infusion of ang II with the&nbsp / MLE did not produce any significant changes in BP or HR when compared to the infusion of the standard drug alone. The co-infusion of phenylephrine with the MLE did not&nbsp / produce any significant change in BP or HR when compared to the values obtained with the infusion of the standard drug alone, in both the absence and presence of prazosin.&nbsp / The co-infusion of dobutamine with T. violacea produced siginificant (p &lt / 0.05) increases in DBP which were associated with significant (p &lt / 0.05) reductions in HR, when&nbsp / compared to the values obtained with the infusion of the standard drug alone. Theco-infusion of atropine with the MLE did not produce any significant change in BP or HR when&nbsp / compared to the values obtained with the infusion of atropine alone. However, the infusion of T. violacea, 20 minutes after pre-treating animals with atropine (5.12 mg/kg) lead to&nbsp / dose dependent significant (p &lt / 0.05) increases in BP, which were associated with dose-dependent increases in HR. The chronic treatment of animals with T. violacea or&nbsp / captropril produced (a) signicant (p &lt / 0.05) reductions in the plasma levels of aldosterone when compared to the values obtained in the vehicle-treated group, (b) produced&nbsp / signifiant (p &lt / 0.05) reduction in BP in the captopril treated group when compared to the vehicle-treated, (c) did not produce any signficant change in BP in the T. violacea-treated&nbsp / group when compared to the vehicle-treated group and (d) did not produce any signifiant change in HR or body weight in any of the groups. The result obtained in this study&nbsp / suggests that T. violacea reduced BP and HR in the SHR. Secondly, the BP and HR reducing effect of the MLE may involve a) the inhibition of the ACE, b) the inhibition of the &beta / 1&nbsp / adrenoceptors, c) the stimulation of the muscarinic receptors and d) the reduction of the levels of aldosternone in plasma. The results also&nbsp / suggest that the MLE may not act&nbsp / through the angiotensin II receptors or the &alpha / 1 adrenergic receptors.&nbsp / </p>

Objective: To evaluate the tendencies of utilization of Angiotensin converting enzyme inhibitors and Angiotensin II receptors antagonists in Lithuania during 2005-2007 years. Methods: MEDLINE database was searched to identify and evaluate all literature relating to pharmacokinetic and pharmacodynamic characteristics of Angiotensin converting enzyme inhibitors and Angiotensin II antagonists. Utilization data of Angiotensin converting enzyme inhibitors (plain and combinations) and Angiotensin II antagonists (plain and combinations) in Lithuania over three years (2005 – 2007) period were obtained from SoftDent, JSC database. The retail prices of agents acting on the Renin-angiotensin-aldosterone selected from Reimbursed Medical Products Reference Prices Lists of 2005, 2006, 2007 years. Drugs were classified according to the Anatomic Therapeutic Chemical system and use was quantified in terms of defined daily doses (ATC/DDD). Consumption of Angiotensin converting enzyme inhibitors (plain and combinations) and Angiotensin II antagonists (plain and combinations) was calculated by DDD methodology and expressed as DDD per 1.000 inhabitants per day. Pharmacoeconomic calculations were done according to cost minimization and reference price methodologies. Results: According to meta-analysis, number of included studies (69 publications) that evaluated various treatment and head-to-head efficacy comparisons found in literature no consistent differential effects of ACEIs versus ARBs on... [to full text] / Tikslas: atlikti Angiotenziną konvertuojančių fermentų inhibitorių ir Angiotenzino II antagonistų suvartojimo tendencijų Lietuvoje analizę 2005 – 2007 metais. Metodai: Duomenys apie Angiotenziną konvertuojančio fermento inhibitorių ir Angiotenzino II antagonistų farmakokinetines ir farmakodinamines savybes buvo surinkti iš MEDLINE elektroninių duomenų šaltinių. Duomenys apie AKF inhibitorių (paprastų ir sudėtinių) ir Angiotenzino II antagonistų (paprastų ir sudėtinių) suvartojimą Lietuvoje per 2005 – 2007 metus gauti iš UAB SoftDent duomenų bazės. Renino-angiotenzino-aldosterono sistemą veikiančių vaistų mažmeninės kainos išrinktos iš Lietuvos kompensuojamų vaistinių preparatų 2005, 2006, 2007 metų kainynų. Vaistai buvo suklasifikuoti pagal anatominę terapinę cheminę (ATC) klasifikaciją. AKFI inhibitorių (paprastų ir sudėtinių) ir Angiotenzino II antagonistų (paprastų ir sudėtinių) suvartojimas buvo vertinamas pagal apibrėžtos dienos dozės (DDD – daily defined dose) metodiką, o duomenys įvertinti pagal DDD skaičių, tenkantį 1000 gyventojų per vieną dieną. AKF inhibitorių (paprastų ir sudėtinių) ir Angiotenzino II antagonistų (paprastų ir sudėtinių) farmakoekonominei analizei atlikti buvo taikytas kainų mažinimo bei standartinės kainos nustatymo metodai. Rezultatai: Vadovaujantis metaanalizių, įvairių klinikinių tyrimų 69 publikacijomis bei išsamia AKF inhibitorių ir Angiotenzino II antagonisų efektyvumo palyginimo analize galima teigti, kad šių vaistų grupių poveikis... [toliau žr. visą tekstą]

<p>Tulbaghia violacea Harv. (Alliaceae) is a small bulbous herb which belongs to the family, Alliaceae, most commonly associated with onions and garlic. In South Africa (SA), this&nbsp / herb has been traditionally used in the treatment of various ailments, including fever, colds, asthma, paralysis, hypertension (HTN) and stomach problems. The aim of this study&nbsp / was to evaluate the effect of methanol leaf extracts (MLE) of T. violacea on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats / &nbsp / and to find out the mechanism(s) by which it acts. The MLE of T. violacea (5 - 150 mg/kg), angiotensin I (ang I, 3.1 - 100 &mu / g/kg), captopril (10 mg/kg), angiotensin II (ang II, 3.1 - 50&nbsp / g/kg), losartan (30 mg/kg), phenylephrine (0.01 &ndash / 0.16 mg/kg), prazosin (1 mg/kg), dobutamine (0.2 &ndash / 10.0 &mu / g/kg), propranolol (0.1 - 12.8 mg/kg), muscarine (0.16 -10 &mu / g/kg),&nbsp / and atropine (0.02 - 20.48 mg/kg) were administered intravenously into male spontaneously hypertensive rats (SHR) weighing between 300 g and 350 g and aged less than 5&nbsp / months. The MLE of T. violacea and/or the standard drugs were infused alone, simultaneously, or separately into each animal. The BP and HR were measured via a pressure&nbsp / transducer connecting the femoral artery and the Powerlab. The vehicle (0.2 mls of a mixture of dimethylsulfoxide and normal saline), T. violacea (60 mg/kg) and captopril (10&nbsp / mg/kg) were injected intraperitoneally into some SHR for 21 days to investigate the chronic effect of these agents on plasma levels of aldosterone. The mean change, the mean&nbsp / of the individual percentage changes and the percentage difference (in mean) observed with each intervention was calculated and statistically analyzed using the Student&rsquo / s t test&nbsp / for significant difference (p &lt / 0.05). The Microsoft Excel software was used for statistical analysis. T. violacea significantly (p &lt / 0.05) reduced the systolic, diastolic, and mean&nbsp / arterial BP / and HR dose-dependently. In a dose-dependent manner, ang I, ang II, phenylephrine significantly (p &lt / 0.05) increased the BP, while propranolol, muscarine and&nbsp / atropine reduced the BP. The increases in BP due to dobutamine were not dose-dependent. In a dose dependent manner, phenylephrine and propranolol reduced the HR, while dobutamine increased the HR. The effect of ang I, ang II, muscarine and atropine on HR were not dose-dependent / with both increases as well as decreases observed with ang&nbsp / I, and II and atropine, while decreases were seen with muscarine. Captopril produced&nbsp / significant (p &lt / 0.05) reduction in BP which were not associated with any change in HR. The co-infusion of ang I with the MLE produced significant (p &lt / 0.05) reduction in BP, which were not associated with significant changes in HR. The co-infusion of ang II with the&nbsp / MLE did not produce any significant changes in BP or HR when compared to the infusion of the standard drug alone. The co-infusion of phenylephrine with the MLE did not&nbsp / produce any significant change in BP or HR when compared to the values obtained with the infusion of the standard drug alone, in both the absence and presence of prazosin.&nbsp / The co-infusion of dobutamine with T. violacea produced siginificant (p &lt / 0.05) increases in DBP which were associated with significant (p &lt / 0.05) reductions in HR, when&nbsp / compared to the values obtained with the infusion of the standard drug alone. Theco-infusion of atropine with the MLE did not produce any significant change in BP or HR when&nbsp / compared to the values obtained with the infusion of atropine alone. However, the infusion of T. violacea, 20 minutes after pre-treating animals with atropine (5.12 mg/kg) lead to&nbsp / dose dependent significant (p &lt / 0.05) increases in BP, which were associated with dose-dependent increases in HR. The chronic treatment of animals with T. violacea or&nbsp / captropril produced (a) signicant (p &lt / 0.05) reductions in the plasma levels of aldosterone when compared to the values obtained in the vehicle-treated group, (b) produced&nbsp / signifiant (p &lt / 0.05) reduction in BP in the captopril treated group when compared to the vehicle-treated, (c) did not produce any signficant change in BP in the T. violacea-treated&nbsp / group when compared to the vehicle-treated group and (d) did not produce any signifiant change in HR or body weight in any of the groups. The result obtained in this study&nbsp / suggests that T. violacea reduced BP and HR in the SHR. Secondly, the BP and HR reducing effect of the MLE may involve a) the inhibition of the ACE, b) the inhibition of the &beta / 1&nbsp / adrenoceptors, c) the stimulation of the muscarinic receptors and d) the reduction of the levels of aldosternone in plasma. The results also&nbsp / suggest that the MLE may not act&nbsp / through the angiotensin II receptors or the &alpha / 1 adrenergic receptors.&nbsp / </p>