Potential Antihypertensive Activity of the Aqueous Extract of Ammi visnaga and its Effect on ACE-2 in Rats.

AIMS: This work aimed to investigate the antihypertensive activity of Ammi visnaga. BACKGROUND: The aqueous extract of Ammi visnaga has traditionally been used to treat hypertension in Morocco. OBJECTIVE: The objective of this investigation was to evaluate the effect of Ammi visnaga aqueous extract (AVAE) on arterial blood pressure, systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP), and heart rate (HR) in normotensive and hypertensive rats. In addition, the effect of the aqueous extract of Ammi visnaga on vasodilatation was assessed in isolated rat aortic rings with functional endothelium pre-contracted with epinephrine EP or KCl. METHODS: AVAE was obtained, and its antihypertensive ability was pharmacologically investigated in L-NAME hypertensive and normotensive rats. The rats received oral AVAE at two selected doses of 70 and 140 mg/kg for six hours (acute experiment) and seven days (sub-chronic). Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. Moreover, the vasorelaxant activity of AESA was performed in thoracic aortic ring rats. In addition, the mechanisms of action involved in the vasorelaxant effect were studied. RESULTS: AVAE lowered blood pressure only in L-Name-induced hypertensive rats. Furthermore, AVAE (0.375-1.375 mg/ml) showed a vasodilator effect in isolated aortic rats. In addition, not all of the medications used in our study were responsible for the signaling pathway. As a result, additional pharmaceuticals are required to confirm the mechanism of this signaling pathway. CONCLUSION: The aqueous extract of Ammi visnaga exerts an interesting antihypertensive activity, which could be mediated through its vasorelaxant activity. The study supports its use as a medicinal plant against hypertension in Morocco.

Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation. / Auswertung der DeGIR-Registerdaten zur endovaskulären Therapie von zerebralen Vasospasmen in Deutschland 2018­2021: Ein Überblick über die aktuelle Versorgungssituation.

BACKGROUND: Evaluation of endovascular therapies for cerebral vasospasm (CVS) documented in the DeGIR registry from 2018-2021 to analyse the current clinical care situation in Germany. METHODS: Retrospective analysis of the clinical and procedural data on endovascular spasm therapies (EST) documented anonymously in the DeGIR registry. We analysed: pre-interventional findings of CTP and consciousness; radiation dose applied, interventional-technical parameters (local medication, devices, angiographic result), post-interventional symptoms, complications and mortality. RESULTS: 3584 patients received a total of 7628 EST (median age/patient: 53 [range: 13-100, IQR: 44-60], 68.2 % women) in 91 (2018), 92 (2019), 100 (2020) and 98 (2021) centres; 5388 (70.6 %) anterior circulation and 378 (5 %) posterior circulation (both involved in 1862 cases [24.4 %]). EST was performed once in 2125 cases (27.9 %), with a mean of 2.1 EST/patient. In 7476 times, purely medicated EST were carried out (nimodipine: 6835, papaverine: 401, nitroglycerin: 62, other drug not specified: 239; combinations: 90). Microcatheter infusions were documented in 1132 times (14.8 %). Balloon angioplasty (BA) (additional) was performed in 756 EST (9.9 %), other mechanical recanalisations in 154 cases (2 %) and stenting in 176 of the EST (2.3 %). The median dose area product during ET was 4069 cGycm² (drug: 4002/[+]BA: 8003 [p < 0.001]). At least 1 complication occurred in 95 of all procedures (1.2 %) (drug: 1.1 %/[+]BA: 4.2 % [p < 0.001]). Mortality associated with EST was 0.2 % (n = 18). After EST, overall improvement or elimination of CVS was found in 94.2 % of cases (drug: 93.8 %/[+]BA: 98.1 % [p < 0.001]). In a comparison of the locally applied drugs, papaverine eliminated CVS more frequently than nimodipine (p = 0.001). CONCLUSION: EST have a moderate radiation exposure and can be performed with few complications. Purely medicated EST are predominantly performed, especially with nimodipine. With (additional) BA, radiation exposure, complication rates and angiographic results are higher or better. When considering drug EST alone, there is evidence for an advantage of papaverine over nimodipine, but a different group size has to be taken into account. In the analysis of EST, the DeGIR registry data are suitable for answering more specific questions, especially due to the large number of cases; for this purpose, further subgroupings should be sought in the data documentation. KEY POINTS: · In Germany, there are currently no guidelines for the endovascular treatment of cerebral vasospasm following spontaneous subarachnoid hemorrhage.. · In addition to oral nimodipine administration endovascular therapy is used to treat cerebral vasospasm in most hospitals.. · This is the first systematic evaluation of nationwide registry data on endovascular treatment of cerebral vasopasm in Germany.. · This real-world data shows that endovascular treatment for cerebral vasospasm has a moderate radiation exposure and can be performed with few complications overall. With (additional) balloon angioplasty, radiation exposure, complication rates and angiographic therapy results are higher or better.. CITATION FORMAT: · Neumann A, Weber W, Küchler J et al. Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation. Fortschr Röntgenstr 2023; 195: 1018 - 1026.

Severe Pulmonary Arterial Hypertension in Healthy Young Infants: Single Center Experience.

OBJECTIVE: We studied the clinical presentation and management of acute pulmonary arterial hypertension (PAH) in healthy young infants, and the effect of thiamine therapy. METHODS: Review of hospital records was conducted for 56 healthy infants (aged below 6 month) who developed sudden onset of pulmonary arterial hypertension as diagnosed on 2D echocardiography, and were admitted at our institution. RESULTS: All patients received supportive care and pulmonary vasodilator therapy, whereas those admitted after Sep-tember, 2019 (n=28) received thiamine in addition, as per the institute's protocol. Overall, complete recovery was seen in 80% (n=45). Infants who died had significantly lower mean pH (7.05 vs 7.27; P=0.001) and serum bicarbonate (9.1 vs 14.9; P=0.007), higher arterial lactate (72.7 vs 61.5; P=0.92), ventricular dysfunction (16 vs 10; P=0.01) and shock (7 vs 9; P=0.008) when compared to those who survived. Baseline characteristics, severity of acidosis and pulmonary hypertension, time taken to recover from PAH, presence of ventricular dysfunction were comparable among those who received thiamine and those who did not receive it. Similarly, recovery (89% vs 71%; P=0.17) and mortality (11% vs 29%) were also comparable between the two groups. CONCLUSIONS: A significant proportion of infants with PAH improve with supportive treatment and pulmonary vasodilator therapy. Thiamine supplementation may not give any additional benefit in these patients.

Identification and characterization of the new generation soluble guanylate cyclase stimulator BAY-747 designed for the treatment of resistant hypertension.

BACKGROUND AND PURPOSE: First-generation soluble guanylate cyclase (sGC) stimulators have shown clinical benefit in pulmonary hypertension (riociguat) and chronic heart failure (vericiguat). However, given the broad therapeutic opportunities for sGC stimulators, tailored molecules for distinct indications are required. EXPERIMENTAL APPROACH: We report the high-throughput screening (HTS)-based discovery of a second generation of sGC stimulators from a novel imidazo[1,2-a]pyridine lead series. An intense medicinal chemistry programme resulted in the discovery of the sGC stimulator BAY 1165747 (BAY-747). The pharmacokinetic profile of BAY-747 was determined in different species, and it was broadly characterized in pharmacological model systems relevant for vasodilatation and hypertension. KEY RESULTS: BAY-747 is a highly potent sGC stimulator in vitro. In addition, BAY-747 showed an excellent pharmacokinetic profile with long half-life and low peak-to-trough ratio. BAY-747 was investigated in experimental in vivo models of malignant and resistant hypertension (rHT). In spontaneously hypertensive (SH) rats, BAY-747 caused a dose-related and long-lasting decrease in mean arterial blood pressure (MAP). Oral treatment over 12 days resulted in a persistent decrease. BAY-747 provided additional benefit when dosed on top of losartan, amlodipine or spironolactone and even on top of triple combinations of frequently used antihypertensive drugs. In a new canine model of rHT, BAY-747 caused a dose-related and long-lasting (>6 h) MAP decrease. CONCLUSION AND IMPLICATIONS: BAY-747 is a potent, orally available sGC stimulator. BAY-747 shows long-acting pharmacodynamic effects with a very low peak-to-trough ratio. BAY-747 could be a treatment alternative for patients with hypertension, especially those not responding to standard-of-care therapy.

Management of neonatal pulmonary hypertension-a survey of neonatal intensive care units in India.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition associated with significant morbidity and mortality. First-line diagnostic and treatment options such as echocardiography and inhaled nitric oxide (iNO) are not routinely available in resource limited settings and alternative treatment modalities need to be utilized. This study was conducted to assess current diagnostic and management strategies used for PPHN in Indian neonatal intensive care units (NICUs). METHODS: A questionnaire in multiple choice question format was sent to practising neonatologists in India via an online survey tool between July to August 2021. Information pertaining to demographic data, diagnostic criteria and management strategies of PPHN was requested. The responses were collated and information processed. RESULTS: There were 118 respondent NICUs (response rate 74%). The majority of neonatal units (65%) admitted an average of 1-3 patients of PPHN per month. Targeted neonatal echocardiography (TnECHO) was practised in 80% of the units. Most common management strategies being followed were pulmonary vasodilators (88.1%), inotropes (85.6%), conventional ventilation (68.6%) and high frequency ventilation (59.3%). The most preferred pulmonary vasodilator was sildenafil (79%) and inotropic agent was milrinone (32%). Only 25% of respondents reported use of iNO. None of the participating units used extracorporeal membrane oxygenation. CONCLUSION: We found wide variability in management practices of PPHN across Indian NICUs. Non-selective pulmonary vasodilators are more widely used than iNO. There is an urgent need for structured TnECHO training programs and evidence based national guidelines for standardized management of PPHN as per availability of resources in India. Additional research on low cost alternative therapies to iNO in Indian settings might be helpful.

Antihypertensive Effect of Euphorbia cheiradenia in Rats.

AIMS: The study aimed to investigate the effect of Euphorbia cheiradenia on blood pressure. BACKGROUND: Euphorbia cheiradenia is a medicinal plant with several medicinal properties. OBJECTIVE: This study aimed to study the vasorelaxant and antihypertensive capacity of the aqueous extract of Euphorbia cheiradenia (E. cheiradenia), and to evaluate its effect on angiotensinconverting enzyme 2 (ACE2). METHODS: The antihypertensive ability of aerial parts of the aqueous extract of E. cheiradenia (AEEC) was investigated in L-NAME-induced hypertensive rats, and its vasorelaxant effect was performed on the isolated thoracic rat aorta. In addition, the possible inhibitory effect of AEEC on ACE2 was also studied. RESULTS: AEEC lowered blood pressure parameters in hypertensive rats. The study of the vasorelaxant activity revealed that AEEC partially relaxed the aortic rings through activation of the KATP channel and inhibition of the ß-adrenergic pathway. Whereas pretreatment of aortic rings with nifedipine, indomethacin, L-NAME, and methylene blue did not attenuate AEEC-induced vasorelaxation. However, AEEC did not affect ACE2 in isolated rat aortas. CONCLUSION: The study showed that aqueous E. cheiradenia extract exhibits significant antihypertensive activity in hypertensive rats.

L-Tartaric Acid Exhibits Antihypertensive and Vasorelaxant Effects: The Possible Role of eNOS/NO/cGMP Pathways.

AIMS: The aim of the study was to investigate the antihypertensive effect of L-Tartaric acid. BACKGROUND: L-Tartaric acid (L-TA) is a well-known weak organic acid that naturally occurs in a wide range of fruits, most notably in grapes, tamarind, and citrus. OBJECTIVE: The present study aimed to assess the effect of acute and subchronic administration of L-TA on blood pressure parameters in normotensive and hypertensive rats as well as its vasorelaxant potency. METHODS: In the current study, the antihypertensive activity of L-TA was pharmacologically studied. L-NAME-induced hypertensive and normotensive rats received L-TA (80 and 240 mg/kg) orally over six hours for the acute experiment and seven days for the subchronic treatment. Thereafter, systolic, diastolic, mean, mid arterial blood pressure, and pulse pressure as well as heart rate were evaluated. In the in vitro experiment, the vasorelaxant ability of L-TA was performed in ratisolated thoracic aorta. RESULTS: An important drop in blood pressure was recorded in L-NAME-induced hypertensives treated with L-TA. This molecule also produced a dose-dependent relaxation of the aorta precontracted with norepinephrine (NEP) and KCl. The study demonstrated that the vasorelaxant capacity of L-TA seems to be exerted through the activation of eNOS/NO/cGMP pathways.

Ammodaucus leucotrichus Acts as an Antihypertensive and Vasorelaxant Agent Through sGC and Prostaglandin Synthesis Pathways.

BACKGROUND: Ammodaucus leucotrichus is a medicinal plant used in traditional medicine to treat various ailments, including hypertension. AIMS: The study aimed to determine the antihypertensive activity of Ammodaucus leucotrichus. OBJECTIVE: The study aimed to investigate the antihypertensive and vasorelaxant activities of the aqueous extract of Ammodaucus leucotrichus fruits (ALAE) in rats. METHODS: ALAE was prepared to study its antihypertensive effect in L-NAME (Nω-L-arginine methyl ester)-induced hypertensive rats and its vasorelaxant activity in isolated thoracic aortas of rats. The acute and subchronic effects of ALAE on systolic, diastolic, mean arterial pressure, and heart rate (HR) were evaluated after oral administration of ALAE (60 and 100 mg/kg body weight) for 6 h for the acute experiment and over 7 days for the subchronic test. Isolated thoracic aortic rings were prepared to examine the vasorelaxant action of ALAE. Several common pharmacological agents were used to test potential pathways implicated in vasorelaxant action. RESULTS: The results showed that ALAE reduced blood pressure parameters (systolic, mean, and diastolic blood pressure) in L-NAME-induced hypertension rats after repeated oral treatment over seven days without affecting normotensive rats. Furthermore, in thoracic aortic rings pre-contracted with epinephrine (EP) (10 µM) or KCl (80 mM), ALAE (0.250-1.625 mg/ml) showed a vasorelaxant effect. In isolated rat thoracic aortas, blockage of soluble guanylyl cyslase with blue methylene (P < 0.01) partially decreased this vasorelaxant effect. In addition, blockage of the prostaglandin synthesis pathway with indomethacin (P<0.05) also reduced the vasorelaxant activity of ALAE. Pretreatment of aortic rings with glibenclamide, propanolol, L-NAME, MLN-4760, or nifedipine did not affect ALAE-induced vasorelaxation. CONCLUSION: Ammodaucus leucotrichus is a prescient medicinal plant, able to act as an antihypertensive agent. Moreover, the results suggest that the extract increased cGMP in NO-independent manner.

Study of the Antihypertensive and Vasorelaxant Activities of Haloxylon scoparium in Rats.

AIMS: The work aimed to study the antihypertensive ability of Haloxylon scoparium. BACKGROUND: Haloxylon scoparium Pomel is used to treat various diseases, including hypertension. OBJECTIVE: This study aimed to evaluate the antihypertensive effect of Haloxylon scoparium (H. scoparium) in hypertensive rats, and to evaluate its probable vasorelaxant activity. MATERIALS AND METHODS: The aqueous extract of Haloxylon scoparium (AEHS) was prepared and used to investigate its antihypertensive ability in L-NAME(Nω-L-arginine methyl ester)-induced hypertensive rats, and its vasorelaxant activity was studied on the isolated thoracic aorta of rats. The acute and subchronic effects of (AEHS) on blood pressure parameters were evaluated after oral administration of AEHS (60 and 100 mg/kg body weight) for 6 h for the acute experiment and for 7 days for the subchronic test. RESULTS: The results indicated that AEHS decreased blood pressure parameters (systolic, mean, and diastolic blood pressure) after repeated oral administration in hypertensive rats without affecting normal rats. In addition, AEHS (375-1250 µg/mL) revealed a vasorelaxant effect in thoracic aortic rings precontracted with norepinephrine (NE) (10 µM) or KCl (80 mM). This effect was partially decreased in the presence of nifedipine by inhibition of the vascular calcium channel pathway in isolated rat thoracic aorta. CONCLUSION: The study demonstrates the beneficial effect of Haloxylon scoparium as an antihypertensive agent. Moreover, this plant exerts vasorelaxant activity via the blockade of Ca2+ channels.

Potential biomedical applications of Araucaria araucana as an antispasmodic, bronchodilator, vasodilator, and antiemetic: Involvement of calcium channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Since pre-Columbian era, the resin of Araucaria araucana tree has been used traditionally for the treatment of ulcers and wounds. Araucaria species have also been used to treat inflammation, respiratory problems, viral infections, ulcers, and rheumatoid, cardiovascular, and neurological disorders. AIMS AND OBJECTIVE: Due to its popular use, the authors aimed to scrutinize the potential of this plant as an antispasmodic and an antiemetic agent. Furthermore broncho- and vasodilatory effects of this plant was explored to rationalize its folkloric uses. MATERIALS AND METHODS: Araucaria araucana crude extract (Aa.Cr) was evaluated in isolated preparations of rabbit jejunum, trachea, aorta, and atria to investigate the antispasmodic, bronchodilator, and vasodilator effects. The potential mechanistic approaches were compared with the standard drug 'verapamil'. The antiemetic activity was determined and compared with the standard drug 'domperidone' via chick emesis model. RESULTS: Aa.Cr dose-dependently relaxed both spontaneous and K+-induced contractions in the isolated jejunum preparations of rabbits. In concentration-response curves of calcium (Ca++), Aa.Cr also triggered the rightward shift like verapamil. Applying carbachol and phenylephrine (1 µM) and K+ (80 mM) to the isolated tracheal and aortic tissue preparation, respectively, resulted in broncho- and vasodilatory activities, respectively which may be due to the inhibition of Ca++ channels. Aa.Cr inhibited atrial force and spontaneous contractions in the rabbit's right atria. Aa.Cr exhibited significant antiemetic activity (P < 0.001 vs. saline) in dose-dependent (50-150 mg/kg) manner like domperidone. In silico molecular docking was performed to investigate the biological targets of purified components of Aa.Cr which revealed that cadinol dominantly targets ß2 receptors to cause bronchodilation, however, eudesmin binds non-specifically to all the selected targets, while secoisolariciresinol mediated high hydrogen bonding with muscarinic receptors (M1 and M3) and Ca++ channels, thus shows the suggested mechanistic pathways of targeted activities. CONCLUSIONS: The results of this study indicates that Aa.Cr may exhibit antispasmodic activity, bronchodilation, and vasodilation by inhibiting voltage-dependent Ca++ channels and release of subcellular calcium. This explains its folkloric use in hypertension, bronchospasms, gastrointestinal spasms, and emesis.

Calcinosis in dermatomyositis: Origins and possible therapeutic avenues.

Calcinosis, insoluble calcium compounds deposited in skin and other tissues, is a crippling sequela of dermatomyositis. Prolonged disease associated with ongoing inflammation, ischemia, repetitive trauma, and certain autoantibodies are associated with calcinosis. Herein, we describe potential pathogenic mechanisms including the role of mitochondrial calcification. There are no widely effective treatments for calcinosis. We review available pharmacologic therapies for calcinosis including those targeting calcium and phosphorus metabolism; immunosuppressive/anti-inflammatory therapies; and vasodilators. Mounting evidence supports the use of various formulations of sodium thiosulfate in the treatment of calcinosis. Although the early institution of aggressive immunosuppression may prevent calcinosis in juvenile dermatomyositis, only limited data support improvement once it has developed. Minocycline can be useful particularly for lesions associated with surrounding inflammation. Powerful vasodilators, such as prostacyclin analogs, may have promise in the treatment of calcinosis, but further studies are necessary. Surgical removal of lesions when amenable is our treatment of choice.

Metabolomics based mechanistic insights to vasorelaxant and cardioprotective effect of ethanolic extract of Citrullus lanatus (Thunb.) Matsum. & Nakai. seeds in isoproterenol induced myocardial infraction.

BACKGROUND: Cardiovascular diseases (CVDs) are a significant cause of morbidity and death in the current world, posing a challenge to both developing and industrialized nation's health systems. Citrullus lanatus (Thunb.) Matsum. & Nakai. seeds have long been utilized to supplement and enhance health and treat cardiovascular illnesses. However, its treatments for CVDs are still unknown. More research is required to fully comprehend the impact of C. lanatus seeds on vasorelaxation and myocardial infractions. PURPOSE: Therefore, an integrated metabolomics profiling technique was used to investigate possible pathways of C. lanatus in isoproterenol (ISO)-induced myocardial infarction (MI). Isoproterenol causes long-term cardiac hypertrophy by causing cardiomyocyte compensatory loss, eventually leading to heart failure. METHODS: In vitro models of vasoconstriction, atrium, and in vivo models of invasive blood pressure measurement and isoproterenol (ISO) induced cardiac hypertrophy in rats were used to understand underlying mechanistic by LC-MS/MS based dynamic metabolomics analysis of the serum and heart samples to be investigated the effect of ethanolic extract of C. lanatus (Cl.EtOH). RESULTS: Cl.EtOH exhibited vasorelaxant, negative chronotropic, and inotropic effects in in-vitro models whereas, a potent hypotensive effect was observed in normotensive rats. The Cl.EtOH protected the animals from ISO-induced myocardial infarction (MI) with therapeutic interventions in left ventricular thickness, cardiomyocyte hypertrophy, mRNA gene expression, biochemical assays, and metabolomic profiling of serum and heart tissues. CONCLUSIONS: For the first time, our study confirmed that C. lanatus seeds (Cl.EtOH) possess significant antihypertensive and prevent ISO-induced myocardial infarction. These findings comprehensively demonstrated mechanistic insights of Cl.EtOH in vasorelaxation and myocardial infarction. The current study provides evidence for further mechanistic studies and the development of C. lanatus seeds as a potential therapeutic intervention for patients with cardiovascular disorders.

Effect of Calamintha officinalis on Vascular Contractility and Angiotensinconverting Enzyme-2.

AIMS: The study aimed to assess the antihypertensive activity of Calamintha officinalis. BACKGROUND: Calamintha officinalis (CO) is a medicinal and aromatic herb as well as an antihypertensive plant that is widely used for its medicinal properties in several regions. OBJECTIVE: This study aimed to evaluate the effect of the aqueous extract of Calamintha officinalis (AECO) on vasorelaxant activity and arterial blood pressure under normal and hypertensive states in rats. Additionally, the effect of AECO on vascular angiotensin-converting enzyme 2 (ACE-2) was assessed. METHODS: In the current study, AECO (100 mg/Kg) was prepared, and its antihypertensive ability was assessed in L-NG-Nitro arginine methyl ester (L-NAME)-induced hypertensive rats. Blood pressure and heart rate were recorded for 6 h for the acute experiment and during seven days for the subchronic treatment. RESULTS: The results indicated that AECO reduced the systolic, diastolic, and mean arterial blood pressure in hypertensive rats. In addition, the study showed that AECO exerts a vasorelaxant ability through the sGC-cGMP induction pathway, vascular cyclooxygenase pathway, and the opening of K+ channels. However, AECO had no inhibitory effect on aortic ACE-2. CONCLUSION: The study illustrates the beneficial action of AECO as an antihypertensive and vasorelaxant agent.

Spergularia marina: a potential source of a novel calcium channel blocker with antihypertensive and diuretic activities.

OBJECTIVE: Spergularia marina (L.) Griseb. (S. marina) is a sub-cosmopolitan species used as traditional phytotherapy based on diverse biological activities. It is native and widespread in the northern hemisphere, though introduced also into the southern hemisphere. The extract of another species 'Spergularia purpurea' has been traditionally used in Morocco against various diseases and S. marina, itself, is a local popular food in South Korea. In this context, we evaluated the potential antihypertensive and diuretic effects of S. marina water and n-butanol extracts in L-NAME-induced hypertensive rats vs. the well-known diuretic, furosemide. MATERIALS AND METHODS: After toxicity studies, selected doses were administered orally daily for one week. Mean arterial blood pressure (MABP), water/electrolyte clearance, renal functions, and serum electrolytes were assessed. Vascular reactivity of isolated aortic rings was evaluated under different incubating settings against various antagonists to unravel the mechanism of action. RESULTS: Both extracts significantly reduced the MABP. Only, the n-butanol fraction exerted a significant aquaresis, increasing electrolyte free-water clearance with a significantly decreased urinary Na+, K+, and C- excretion. The water extract significantly augmented the ACh-induced relaxation and attenuated the NE-induced aortic rings' contractile response. It also exhibited a direct relaxant effect on the NE-precontracted rings with intact or denuded endothelium. Blocking the vascular calcium channels by preincubation with nifedipine prevented the S. marina-induced relaxation, denoting a calcium channel blocking activity. CONCLUSIONS: The vasorelaxant and the differential diuretic effects of both extracts introduce S. marina as a potential novel antihypertensive agent with calcium channel blocking activity. To enrich cardiovascular therapeutics, human studies to confirm the efficacy and safety of S. marina in hypertension are warranted. GRAPHICAL ABSTRACT: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract.jpg.

Radiation exposure in the intra-arterial nimodipine therapy of subarachnoid hemorrhage related cerebral vasospasm.

The selective intra-arterial nimodipine application for the treatment of cerebral vasospasm (CVS) in patients after spontaneous subarachnoid hemorrhage (sSAH) is widely employed. The purpose of this study is to examine the radiation exposure and to determine local diagnostic reference levels (DRLs) of intra-arterial nimodipine therapy. In a retrospective study design, DRLs and achievable dose (AD) were assessed for all patients undergoing (I) selective intra-arterial nimodipine application or (II) additional mechanical angioplasty for CVS treatment. Interventional procedures were differentiated according to the type of procedure and the number of probed vessels. Altogether 494 neurointerventional procedures of 121 patients with CVS due to sSAH could be included. The radiation exposure indices were distributed as follows: (I) DRL 74.3 Gy·cm2, AD 59.8 Gy·cm2; (II) DRL 128.3 Gy·cm2, AD 94.5 Gy·cm2. Kruskal-Wallis test confirmed significant dose difference considering the number of probed vessels (p< 0.001). The mean cumulative dose per patient was 254.9 Gy·cm2(interquartile range 88.6-315.6 Gy·cm2). The DRLs of intra-arterial nimodipine therapy are substantially lower compared with DRLs proposed for other therapeutic interventions, such as thrombectomy or aneurysm coiling. However, repeated therapy sessions are often required, bearing the potential risk of a cumulatively higher radiation exposure.

Vericiguat: A Novel Oral Soluble Guanylate Cyclase Stimulator for the Treatment of Heart Failure.

OBJECTIVE: To review the efficacy and safety of vericiguat indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following hospitalization or need for outpatient intravenous diuretics in adult patients with chronic symptomatic HF and ejection fraction (EF) less than 45%. DATA SOURCES: A literature search through MEDLINE with search terms MK1242, BAY 1021189, and vericiguat was conducted. Product labeling and English-language studies assessing pharmacokinetics, pharmacodynamics, efficacy, or safety of vericiguat were included. STUDY SELECTION AND DATA EXTRACTION: Preclinical and clinical studies describing the efficacy and safety of vericiguat were included. DATA SYNTHESIS: The phase 3 VICTORIA clinical trial demonstrated a lower composite primary outcome of death from cardiovascular causes or first hospitalization in the vericiguat group compared to placebo. Total hospitalizations for HF in the vericiguat group were significantly less compared to placebo. The composite secondary outcome of death from any cause or first HF hospitalization was significantly less in the vericiguat group. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The addition of vericiguat offers a new treatment option for those in whom rehospitalization or recurrent outpatient intravenous diuretic treatment is a concern. Given high rates of nonadherence in HF patients, vericiguat represents an additional treatment option, especially for patients who do not tolerate available HF therapies. CONCLUSION: Vericiguat is a novel soluble guanylate cyclase stimulator that is safe and effective for reducing the risk of cardiovascular death and HF hospitalization in adults with symptomatic chronic HF and reduced EF.

Continuous intra-arterial nimodipine infusion as rescue treatment of severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

Severe refractory cerebral vasospasm (CV) is a major cause of disability and death in patients with aneurysmal subarachnoid hemorrhage (SAH). One rescue therapy in selected patients is intra-arterial nimodipine, either given as a single shot or as continuous infusion. To evaluate treatment efficacy, we analyzed outcome factors such as the incidence of craniectomy, ventriculo-peritonial (VP) shunting, and tracheotomy after intra-arterial nimodipine infusion. We retrospectively analyzed the rates of cerebral infarction, decompressive craniectomy, VP shunting, and tracheotomy in patients with severe CV after SAH. Three different patient groups were compared: group 1 had only been treated with oral nimodipine and hypervolemic hypertensive therapy (HHT) (2006-2010), group 2 with a single shot of intra-arterial nimodipine (SSN) in addition to oral conservative treatment (2006-2010), and group 3 with continuous intra-arterial nimodipine (CIAN) (2011-2017). The incidence of cerebral infarction was significantly lower in CIAN group (p = 0.005) than in conservative and SSN group. The indication for consecutive decompressive craniectomy was significantly lower in CIAN group in comparison with the conservative group (p = 0.018). The rates of VP shunting and tracheotomy were significantly higher in the CIAN group than in the conservative group (p = 0.028 for VP, and p = 0.003 for tracheotomy). The significantly lower rate of craniectomy in the CIAN group was most probably attributable to the significantly lower rate of CV-induced infarction. The higher rate of tracheotomy reflects more extensive sedation and the need of longer stays on the intensive care unit. Thus, the effect on long-term neurological outcome and quality of life has to be evaluated separately.

Mechanisms of Action of Nutritionally Rich Hibiscus sabdariffa's Therapeutic Uses in Major Common Chronic Diseases: A Literature Review.

Hibiscus sabdariffa, this beverage has been used for millennia as both a delicious cultural beverage and an ancient medicinal therapy. In recent years, many studies have investigated the uses and mechanisms of action of Hibiscus sabdariffa to treat common chronic diseases. In this literature review, we place the spotlight on Hibiscus sabdariffa's medical effect on common chronic diseases, the flower commonly used to make hibiscus tea. The databases PubMed, MEDLINE, Clinical Key, and CINAHL were searched for studies related to Hibiscus sabdariffa's compounds, antioxidative and anti-inflammatory features, mechanism of action on common chronic diseases including hypertension, hyperlipidemia, obesity, diabetes, and Alzheimer's disease. Hibiscus sabdariffa antihypertensive potentials originate from the vasodilator activity, diuretic efficacy, functionality as an ACE inhibitor, adipocyte differentiation inhibitor, heart rate reduction ability, and anti-inflammatory mechanistic. The antihyperlipidemic effect is dose-dependent and stems from the antioxidative effect and the activation of AMPK through phosphorylation and the inhibition of regulatory adipogenic transcription factors PPAR-γ, C/EBP-α, and SREBP-1c, which altogether results in lipid-lowering effect. As an antihyperglycemic, Hibiscus sabdariffa serves as anti-insulin resistance by inhibition of the phosphorylation of IRS-1 beside a similar effect to gliptins. Finally, Hibiscus sabdariffa was proven to protect against neuroinflammation in microglial cell culture exposed to LPS by decreasing IL-1, IL-6, TNF-α expression, and the protective effect against glucotoxicity, improve memory function by inhibiting the formation of hyperphosphorylated tau proteins in the mouse brain. Regular consumption of hibiscus tea or extract is beneficial for a reduction in chronic disease risk and diagnosis.Key teaching pointsHibiscus sabdariffa, or hibiscus, has been used for millennia as both a delicious cultural beverage and an ancient medicinal therapy. Recent studies have investigated the uses of Hibiscus sabdariffa to treat common chronic diseases.Its antihypertensive potential originates from the vasodilator activity, diuretic efficacy, functionality as an ACE inhibitor, adipocyte differentiation inhibitor, heart rate reduction ability, and anti-inflammatory mechanistics.The antihyperlipidemic effect is dose-dependent and stems from the antioxidative effect and the activation of AMPK through phosphorylation and also the inhibition of regulatory adipogenic transcription factors PPAR-γ, C/EBP-α and SREBP-1c which all together results in lipid-lowering effect.As an antihyperglycemic, Hibiscus sabdariffa serves as anti-insulin resistance by inhibition of the phosphorylation of IRS-1 beside the similar effect to gliptins.Hibiscus sabdariffa was proven to protect against neuroinflammation in microglial cell culture exposed to LPS by decreasing IL-1, IL-6, TNF-α expression, and the protective effect against glucotoxicity, improve memory function by inhibiting the formation of hyperphosphorylated tau proteins in the mouse brain.

Integrative Bioinformatics approaches to therapeutic gene target selection in various cancers for Nitroglycerin.

Integrative Bioinformatics analysis helps to explore various mechanisms of Nitroglycerin activity in different types of cancers and help predict target genes through which Nitroglycerin affect cancers. Many publicly available databases and tools were used for our study. First step in this study is identification of Interconnected Genes. Using Pubchem and SwissTargetPrediction Direct Target Genes (activator, inhibitor, agonist and suppressor) of Nitroglycerin were identified. PPI network was constructed to identify different types of cancers that the 12 direct target genes affected and the Closeness Coefficient of the direct target genes so identified. Pathway analysis was performed to ascertain biomolecules functions for the direct target genes using CluePedia App. Mutation Analysis revealed Mutated Genes and types of cancers that are affected by the mutated genes. While the PPI network construction revealed the types of cancer that are affected by 12 target genes this step reveals the types of cancers affected by mutated cancers only. Only mutated genes were chosen for further study. These mutated genes were input into STRING to perform NW Analysis. NW Analysis revealed Interconnected Genes within the mutated genes as identified above. Second Step in this study is to predict and identify Upregulated and Downregulated genes. Data Sets for the identified cancers from the above procedure were obtained from GEO Database. DEG Analysis on the above Data sets was performed to predict Upregulated and Downregulated genes. A comparison of interconnected genes identified in step 1 with Upregulated and Downregulated genes obtained in step 2 revealed Co-Expressed Genes among Interconnected Genes. NW Analysis using STRING was performed on Co-Expressed Genes to ascertain Closeness Coefficient of Co-Expressed genes. Gene Ontology was performed on Co-Expressed Genes to ascertain their Functions. Pathway Analysis was performed on Co-Expressed Genes to identify the Types of Cancers that are influenced by co-expressed genes. The four types of cancers identified in Mutation analysis in step 1 were the same as the ones that were identified in this pathway analysis. This further corroborates the 4 types of cancers identified in Mutation analysis. Survival Analysis was done on the co-expressed genes as identified above using Survexpress. BIOMARKERS for Nitroglycerin were identified for four types of cancers through Survival Analysis. The four types of cancers are Bladder cancer, Endometrial cancer, Melanoma and Non-small cell lung cancer.

Trimetazidine an emerging paradigm in renal therapeutics: Preclinical and clinical insights.

Trimetazidine (TMZ) is a well-known anti-ischemic agent used for the treatment of angina pectoris. In the past decades, the efficacy of this drug has been tested in a wide range of kidney injuries, including drug-induced nephrotoxicity (DIN), radio-contrast agent-induced nephropathy, and surgically induced renal ischemic injury. TMZhas renoprotective effects by attenuating oxidative stress, inflammatory cytokine release, maintaining oxygen and energy balance. Moreover, TMZ administration prevented kidney graft rejection in the porcine model by suppressing the infiltration of mononuclear cells, preserving mitochondrial functions, and maintaining Ca+ homeostasis. In DIN and diabetic kidney diseases,TMZ treatment prevents renal injury by inactivating immune cells, attenuating renal fibrosis, inflammation, apoptosis, and histological abnormalities. Interestingly, the clinical therapeutic efficacy of TMZ has also been documented in pre-existing kidney disease patients undergoing contrast exposure for diagnostic intervention. However, the mechanistic insights into the TMZ mediated renoprotective effects in other forms of renal injuries, including type-2 diabetes, drug-induced nephrotoxicity, and hypertension-induced chronic kidney diseases, remain uninvestigated and incomplete. Moreover, the clinical utility of TMZ as a renoprotective agent in radio-contrast-induced nephrotoxicity needs to be tested in a large patient population. Nevertheless, the available pieces of evidence suggest that TMZ is a promising and emerging renal therapy for the treatment and management of kidney diseases of variable etiologies. This review discusses the various pre-clinical and clinical findings and provides mechanistic insights into the TMZ mediated beneficial effects in various kidney diseases.