Efektivitas Daun Sirsak (Annona muricata Linn) terhadap Penurunan Tekanan Darah Pada Hipertensi

Pendahuluan: Hipertensi merupakan salah satu penyakit tidak menular yang sering disebut sebagai “silent killer” (pembunuh diam-diam) yang dapat didefinisikan dengan suatu kondisi dimana pembuluh darah memiliki tekanan darah tinggi (tekanan darah sistolik > 140 Daun sirsak sering digunakan sebagai pengobatan alternatif hipertensi. Kandungan daun sirsak yang diperkirakan dapat menurunkan tekanan darah adalah ion kalium. Tujuan: mengetahui efektivitas daun sirsak (Annona muricata Linn) terhadap penurunan tekanan darah pada hipertensi. Metode: Menggunakan studi literatur dari jurnal baik nasional maupun internasional dengan cara meringkas topik pembahasan dan membandingkan hasil yang disajikan dalam setiap artikel. Hasil: Ion kalium mempunyai beberapa mekanisme dalam menurunkan tekanan darah, yaitu memperlemah kontraksi miokardium, meningkatkan pengeluaran natrium dari dalam tubuh, menghambat pengeluaran renin, menyebabkan vasodilatasi, dan menghambat vasokontriksi endogen. Kadar kalium yang tinggi dapat meningkatkan eksresi natrium, sehingga dapat menurunkan volume darah dan tekanan darah. Flavonoid bekerja sebagai ACE inhibitor yang akan menghambat perubahan AI menjadi AII sehingga menurunkan sekresi hormon antidiuretik (ADH) yang membuat jumlah sekresi urin meningkat dan banyak garam (NaCl) yang dikeluarkan akhirnya mengakibatkan penurunan tekanan darah. Vitamin C juga berperan dalam menurunkan tekanan darah, karna dapat memodulasi pengeluaran nitric oxide. Kesimpulan: pemberian daun sirsak dapat menurunkan kadar tekanan darah pada hipertensi

Evaluation of the effectiveness of drug treatment in patients with arterial hypertension and insomnia

Objective: chronic sleep disturbance is a comorbid condition with arterial hypertension, often combined with affective disorders, anxiety, depression. Forced sleep deprivation in patients with hypertension indicates a high activity of the renin‑angiotensin‑aldosterone system (RAAS) and desynchronosis of biological rhythms caused by a probable deficit in melatonin secretion during the night. Timely elimination of any pathological process associated with insomnia and arterial hypertension (AH) in the early stages of its development is a prerequisite for the effectiveness of therapy. Therefore, initial therapy should help neutralize the adverse effects of RAAS and improve the 24‑hour blood pressure (BP) profile. The aim of this study was to determine the therapeutic effect of monotherapy with an angiotensin converting enzyme (ACE) inhibitor, As well as in combination with a synthetic analogue of melatonin, on the course of hypertension and parameters of systemic hemodynamics in patients with first degree hypertension with insomnia at the onset of the disease. Combined therapy with an ACE inhibitor and a synthetic analogue of MT in patients with hypertension and insomnia was accompanied by an improvement in the clinical state, achievement of the target blood pressure level in most patients, positive dynamics of central blood pressure parameters and indicators reflecting the rigidity of peripheral arteries.

COVID-19: A New Horizon in Congenital Heart Diseases

Objective: Previous studies have demonstrated that both children and adult patients with a history of congenital heart disease (CHD) are at high risk for coronavirus disease 2019 (COVID-19) infection. This study investigates the status of COVID-19 infection among children undergoing surgical repair within the past 2 years.Methods: All alive patients operated on in a tertiary referral center between March 2018 and March 2020 were recruited in the present study. Detailed demographics, past medical and surgical history, and physical examination were reviewed for each patient. During the COVID-19 pandemic, data regarding the patient's status were collected by telephone survey from April 15 to April 30, 2020.Results: A total number of 210 patients are analyzed in this study. Participants' median age was 21.59 months [interquartile range (IQR) = 12–54.67], and 125 (59.5%) were female. The median interval between surgery and COVID-19 assessment was 305 days (IQR = 215–400). In addition, 67 (32%) patients used angiotensin receptor blocker (ARB)/angiotensin-converting enzyme (ACE) inhibitor (spironolactone and/or captopril). Sixteen patients (7.6%) were symptomatic and had positive chest CT results and/or RT-PCR compared to the previously reported prevalence of COVID-19 among the pediatric population (2.4% of children with <18 years of age); the prevalence of COVID-19 among the patients operated on due to CHD in the present study was significantly higher (p = 0.00012). Two patients were admitted to the intensive care unit (ICU); one patient was discharged 2 weeks later with acceptable status, and one patient died 2 days after ICU admission due to cardiac and respiratory arrest and myocarditis. The complexity of the underlying cardiac disorders was not different between patients with low risk (p = 0.522), suspicious patients (p = 0.920), and patients positive for COVID-19 (p = 0.234). The ARB/ACE inhibitor consumption was not associated with the COVID-19 infection [p = 0.527, crude odds ratio (OR) = 1.407, 95% CI = 0.489–4.052].Conclusion: Children with a history of previous CHD surgery are more susceptible to infections, especially those infections with pulmonary involvements, as the lung involvement could cause worsening of the patient's condition by aggravating pulmonary hypertension. The results of the current study indicate that these patients are more prone to COVID-19 infection compared to the healthy children population.

Association of hypertension with mortality in patients hospitalised with COVID-19

ObjectiveTo assess whether hypertension is an independent risk factor for mortality among patients hospitalised with COVID-19, and to evaluate the impact of ACE inhibitor and angiotensin receptor blocker (ARB) use on mortality in patients with a background of hypertension.MethodThis observational cohort study included all index hospitalisations with laboratory-proven COVID-19 aged ≥18 years across 21 Australian hospitals. Patients with suspected, but not laboratory-proven COVID-19, were excluded. Registry data were analysed for in-hospital mortality in patients with comorbidities including hypertension, and baseline treatment with ACE inhibitors or ARBs.Results546 consecutive patients (62.9±19.8 years old, 51.8% male) hospitalised with COVID-19 were enrolled. In the multivariable model, significant predictors of mortality were age (adjusted OR (aOR) 1.09, 95% CI 1.07 to 1.12, p<0.001), heart failure or cardiomyopathy (aOR 2.71, 95% CI 1.13 to 6.53, p=0.026), chronic kidney disease (aOR 2.33, 95% CI 1.02 to 5.32, p=0.044) and chronic obstructive pulmonary disease (aOR 2.27, 95% CI 1.06 to 4.85, p=0.035). Hypertension was the most prevalent comorbidity (49.5%) but was not independently associated with increased mortality (aOR 0.92, 95% CI 0.48 to 1.77, p=0.81). Among patients with hypertension, ACE inhibitor (aOR 1.37, 95% CI 0.61 to 3.08, p=0.61) and ARB (aOR 0.64, 95% CI 0.27 to 1.49, p=0.30) use was not associated with mortality.ConclusionsIn patients hospitalised with COVID-19, pre-existing hypertension was the most prevalent comorbidity but was not independently associated with mortality. Similarly, the baseline use of ACE inhibitors or ARBs had no independent association with in-hospital mortality.

Angioedema Caused by Drugs That Prevent the Degradation of Vasoactive Peptides: A Pharmacovigilance Database Study

Angioedema results from the decreased degradation of vasoactive peptides such as substance P and bradykinin. In this study, we sought to clarify whether dipeptidyl peptidase-4 (DPP-4) and angiotensin-converting enzyme (ACE) inhibitors that suppress the degradation of substance P and bradykinin are involved in angioedema onset. We calculated information coefficients (ICs) by performing a disproportionality analysis to evaluate DPP-4/ACE inhibitor-induced angioedema using the Japanese Adverse Drug Event Report (JADER) database. No angioedema signals were detected for DPP-4 inhibitors; however, a signal was detected for ACE inhibitors (IC: 2.42, 95% confidence interval (CI): 2.19 to 2.65). Of the patients treated with DPP-4 inhibitors, four developed drug-induced angioedema in combination with ACE inhibitors, and all were taking vildagliptin. Signals were detected for enalapril (IC: 2.39, 95% CI: 2.06 to 2.71), imidapril (IC: 2.83, 95% CI: 2.38 to 3.27), lisinopril (IC: 2.28, 95% CI: 1.55 to 3.00), temocapril (IC: 1.35, 95% CI: 0.29 to 2.40), and trandolapril (IC: 1.57, 95% CI: 0.19 to 2.95). Both inhibitors inhibited the degradation of substance P and bradykinin and were thus expected to cause angioedema. However, no signal of angioedema was detected with the DPP-4 inhibitors, in contrast to some ACE inhibitors. This study found that ACE inhibitors and DPP-4 inhibitors, which inhibit the degradation of substance P and bradykinin, tended to have different effects on the onset of angioedema in clinical practice.

Angiotensin II and the Renal Hemodynamic Response to an Isolated Increased Renal Venous Pressure in Rats

Elevated central venous pressure increases renal venous pressure (RVP) which can affect kidney function. We previously demonstrated that increased RVP reduces renal blood flow (RBF), glomerular filtration rate (GFR), and renal vascular conductance (RVC). We now investigate whether the RAS and RBF autoregulation are involved in the renal hemodynamic response to increased RVP. Angiotensin II (ANG II) levels were clamped by infusion of ANG II after administration of an angiotensin-converting enzyme (ACE) inhibitor in male Lewis rats. This did not prevent the decrease in ipsilateral RBF (−1.9±0.4ml/min, p&lt;0.05) and GFR (−0.77±0.18ml/min, p&lt;0.05) upon increased RVP; however, it prevented the reduction in RVC entirely. Systemically, the RVP-induced decline in mean arterial pressure (MAP) was more pronounced in ANG II clamped animals vs. controls (−22.4±4.1 vs. −9.9±2.3mmHg, p&lt;0.05), whereas the decrease in heart rate (HR) was less (−5±6bpm vs. −23±4bpm, p&lt;0.05). In animals given vasopressin to maintain a comparable MAP after ACE inhibition (ACEi), increased RVP did not impact MAP and HR. RVC also did not change (0.018±0.008ml/minˑmmHg), and the reduction of GFR was no longer significant (−0.54±0.15ml/min). Furthermore, RBF autoregulation remained intact and was reset to a lower level when RVP was increased. In conclusion, RVP-induced renal vasoconstriction is attenuated when ANG II is clamped or inhibited. The systemic effect of increased RVP, a decrease in HR related to a mild decrease in blood pressure, is attenuated also during ANG II clamp. Last, RBF autoregulation remains intact when RVP is elevated and is reduced to lower levels of RBF. This suggests that in venous congestion, the intact RBF autoregulation could be partially responsible for the vasoconstriction.

The Chemical Compounds of Flacourtia rukam Leaves and Their Inhibition of Angiotensin-converting Enzyme (ACE) Activity

Flacourtia rukam is a plant popular among people to treat hypertension, especially the Musi Banyuasin of south Sumatera, Indonesia. Isolation and identification of chemical compounds from F. rukam leaves and evaluation of their effects on antihypertensive activity have been conducted. Isolation of chemical compounds using chromatographic methods and identification using spectroscopic methods were compared with the reported data. The drug’s effects on antihypertension were determined using the angiotensin converting enzyme (ACE) inhibitory method. Two compounds were first reported and isolated from the leaves of F. rukam and identified as apigenin (1) and lupeol (2). These compounds were demonstrated to be effective in treating antihypertension with IC50 656.51 ± 1.55 µg/mL for apigenin and 15.12 ± 0.72 µg/mL for lupeol. It can be concluded that F. rukam leaves is a potential ACE inhibitor can be explored further as an effective antihypertensive agent.

Interactive Effects of Enalapril Administration and Novel HIIT Wheel-Bed Training in Aged Rats

Introduction: Growing research suggests that aerobic high-intensity interval training (HIIT) improves cardiovascular function and physical performance compared with moderate intensity continuous training (MICT). However relatively few animal models of HIIT are available to inform about the benefits of this exercise—particularly among older animals. In addition, there is little evidence for how HIIT training interacts with adjuvant pharmacological therapies known to enhance the impact of MCIT in older individuals such as Angiotensin Converting Enzyme (ACE) Inhibitors.Purpose: The aim of the present study was to establish a HIIT protocol in aged rats based on forced running wheel-bed, and to subsequently (1) establish the feasibility of the HIIT protocol in a proof-of-concept study evaluating interactions between HIIT and (2) the result of combining HIIT + ACE inhibitor treatment using the ACE inhibitor enalapril.Methods: Two groups of rats were used in this study. The feasibility of using wheel-bed for HIIT training was tested in group one (15- and 30-month-old male rats). In the second group, 37 24-month-old Fisher 344 x Brown Norway male rats were randomly divided into four subgroups: control, enalapril, HIIT training group, and HIIT training combined with enalapril administration. The training and administration lasted for 4 weeks. After the intervention, locomotor activity, exercise tolerance, and grip strength were tested.Results: Our feasibility study suggested that middle-aged and aged rats were able to successfully complete the HIIT training. In our intervention study, HIIT training alone, regardless of adjuvant enalapril intervention, did raise treadmill exercise tolerance vs. the sedentary condition. Measures of healthspan were not negatively impacted by HIIT training.Conclusion: The novel HIIT protocol based on forced running wheel-bed was successfully employed in aged rats. We conclude that future studies should compare the results and of multi-modal intervention strategies which include both HIIT and MICT in combination with adjuvant therapies such as enalapril to improve exercise tolerance and other global indices of healthspan.