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Response teams, via the rapid response system (RRS), are activated when a patient's condition deteriorates; respiratory, neurological, or cardiac diseases are precursors to unexpected in-hospital cardiac arrest or death. In December 2019, our hospital introduced the RRS to reduce serious adverse events. Herein, we report a case where RRS was initiated twice for a patient who developed septic shock due to cervical necrotizing fasciitis and non-occlusive mesenteric ischemia (NOMI) after the septic shock. In August 2021, a male in his 70 s developed facial swelling, difficulty opening his mouth, and difficulty with oral intake. We observed necrotic skin on the face, soft tissue swelling in the neck, and hypotension. The RRS was initiated, and the patient was immediately admitted to the intensive care unit (ICU) where he was diagnosed with septic shock and necrotizing fasciitis of the neck. The patient underwent surgical necrotic lesion debridement and incisional drainage under general anesthesia. After weaning from shock, owing to his hypotensive and hemorrhagic status, the RRS was requested again. The patient was re-admitted to the ICU and diagnosed with NOMI. His general condition improved, and he was discharged on day 47. [ABSTRACT FROM AUTHOR]

Background: Obtaining intravenous access in hypotensive patients is challenging and may critically delay resuscitation. The Graduated Vascular Access for Hypotensive Patient (GAHP) protocol leverages intraosseous fluid boluses to specifically dilate proximal veins. This study aims to evaluate the efficacy of GAHP in maximizing venous targets through early distal intraosseous access and a small fluid bolus. Methods: This was a prospective randomized cadaveric pilot study to evaluate extremity venous engorgement during intraosseous infusion. Cadavers (n = 23) had an intraosseous needle inserted into four sites: distal radius, proximal humerus, distal femur, and distal tibia. Intraosseous saline was rapidly infused, venous optimization was measured using real-time ultrasound. Primary outcome was maximum vessel circumference increase with intraosseous infusion. Secondary outcomes were: time to maximum circumference, and infusion volume required. Statistical analyses included Levene’s test for equality of variances, Wilcoxon signed-rank test, and generalized estimating equation. Results: There was a significant mean increase of 1.03 cm (95% CI 0.86, 1.20), representing a difference of 102%. We found no significant difference in time to optimize vessel circumference across sites, but volume required significantly differed. Conclusion: GAHP quickly and effectively increased the circumference of anatomically adjacent veins. Anatomical sites did not differ on time to reach maximum enlargement of vessels following intraosseous infusion but did differ in terms of volume required to maximize vessel circumference. Further research is needed using live, hypotensive patients.

Tree and shrub barks have been used as folk medicine by numerous cultures across the globe for millennia, for a variety of indications, including as vasorelaxants and antispasmodics. Here, using electrophysiology and myography, we discovered that the KCNQ5 voltage-gated potassium channel mediates vascular smooth muscle relaxant effects of barks used in Native American folk medicine. Bark extracts (1%) from Birch, Cramp Bark, Slippery Elm, White Oak, Red Willow, White Willow, and Wild Cherry each strongly activated KCNQ5 expressed in Xenopus oocytes. Testing of a subset including both the most and the least efficacious extracts revealed that Red Willow, White Willow, and White Oak KCNQ-dependently relaxed rat mesenteric arteries; in contrast, Black Haw bark neither activated KCNQ5 nor induced vasorelaxation. Two compounds common to the active barks (gallic acid and tannic acid) had similarly potent and efficacious effects on both KCNQ5 activation and vascular relaxation, and this together with KCNQ5 modulation by other tannins provides a molecular basis for smooth muscle relaxation effects of Native American folk medicine bark extracts.

Desmodium canum is a perennial herb that grows wildly in many territories. In these regions, the leaves, stems and roots of the plant are employed in traditional tonics and teas for their potential medicinal properties. This review aims at compiling and documenting the botany, traditional uses, phytochemistry and pharmacological effects of the plant, along with its potential medicinal applications. A literature review and analysis was conducted to report on the studies that highlighted the traditional and pharmacological applications of the plant, D. canum. The use of the plant is based on folkloric claims with a wealth of anecdotal reports on its health benefits. Recently, studies have added credence to its use in the treatment of a variety of illnesses. There is overwhelming evidence that supports several pharmacological properties of the plant, including its hypoglycaemic, anti-diabetic, antimicrobial, hypotensive androgenic and antioxidant properties. Furthermore, bioactive compounds have been isolated from the plant's extracts with potencies rivalling that of modern medicine. Given the numerous bioactivities of the plant, it is being postulated that compounds (or their derivatives) may be effective in combatting both physiological and pathogenic diseases such as diabetes and pneumonia, respectively. The review underscores the multifaceted pharmacological nature of Desmodium canum and reports on its potential applications in medicine. Potentially, with additional studies, the naturally isolated compounds can be incorporated in both nutraceuticals and pharmaceuticals to improve the availability of treatment options for several illnesses. [ABSTRACT FROM AUTHOR]

Background/aimsTea, produced from the evergreen Camellia sinensis, has reported therapeutic properties against multiple pathologies, including hypertension. Although some studies validate the health benefits of tea, few have investigated the molecular mechanisms of action. The KCNQ5 voltage-gated potassium channel contributes to vascular smooth muscle tone and neuronal M-current regulation.MethodsWe applied electrophysiology, myography, mass spectrometry and in silico docking to determine effects and their underlying molecular mechanisms of tea and its components on KCNQ channels and arterial tone.ResultsA 1% green tea extract (GTE) hyperpolarized cells by augmenting KCNQ5 activity >20-fold at resting potential; similar effects of black tea were inhibited by milk. In contrast, GTE had lesser effects on KCNQ2/Q3 and inhibited KCNQ1/E1. Tea polyphenols epicatechin gallate (ECG) and epigallocatechin-3-gallate (EGCG), but not epicatechin or epigallocatechin, isoform-selectively hyperpolarized KCNQ5 activation voltage dependence. In silico docking and mutagenesis revealed that activation by ECG requires KCNQ5-R212, at the voltage sensor foot. Strikingly, ECG and EGCG but not epicatechin KCNQ-dependently relaxed rat mesenteric arteries.ConclusionKCNQ5 activation contributes to vasodilation by tea; ECG and EGCG are candidates for future anti-hypertensive drug development.

Dromedary camels (Camelus dromedarius) inhabit not only arid areas but are among common domestic animals that are normally kept for numerous uses. It's raw milk (CM) is believed to have exceptional nutraceutical value in addition to it's other uses similar to camel itself. This study aimed to evaluate hypotensive efficacy of raw CM within context of chemical induced hypertension model in albino rats. Rats received the chemical; L-NAME (50 mg/kg body weight/day, p.o.) and amlodipine (10 mg/kg/day, p.o.) as negative and positive controls for 4 weeks. Rats of treatment group received concurrently L-NAME (50 mg/kg body weight /day, p.o.) and raw milk of camel at (100, 300, and 500 mg/kg body weight/day p.o.) respectively for 4 weeks. Result showed significant decrease (p < 0.001) in treatment relative to negative control in all measured parameters viz systolic, diastolic and mean arterial blood pressures in accordance to the used dosages. Also elevated levels of liver/kidney biomarkers in negative control became reduced compared to normal and positive controls courtesy of CM treatment. In conclusion, obtained data revealed CM to be effective in controlling hypertension. The bioactive constituents present in CM appeared likely to be responsible for the observed effect of antioxidant action and ACE inhibition. Evidence is thus provided from research findings that raw CM can afford efficient hypotensive effect. [ABSTRACT FROM AUTHOR]

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Oxytocin is a neurohormone that is routinely administered to patients during dilation and evacuation procedures (D&E) to control bleeding despite minimal evidence in support of this common practice. In this study, the authors sought to evaluate patients with hypotension after receiving oxytocin during D&E procedures. The secondary data from a double-blind, randomized, placebocontrolled trial involving 112 patients who underwent a D&E at 18-24 weeks gestation and prophylactically received an intravenous bolus of either 30 units of oxytocin in 500 mL of normal saline or 500 mL of saline alone at the start of the procedure were analyzed. Anesthesia providers measured blood pressure before, at the time of, and after study medication administration in 5-minute increments until the end of the procedure. No differences in demographic characteristics or mean blood pressure between the 2 groups were observed. The proportion of hypotensive patients was not statistically different at 5 minutes following fluid bolus (oxytocin 25% versus placebo 13%, P=.09). The proportion of hypotensive patients was similar by 10 minutes (oxytocin 20% versus placebo 16%, P=.62). A sample size of 112 provided the ability to detect a 23% difference in the proportion of patients who experienced hypotension (2-sided 95% CI, power of 80%). These findings suggest that oxytocin may have a transient hypotensive effect. [ABSTRACT FROM AUTHOR]

Introduction: Minoxidil, traditionally used as an antihypertensive, is now widely used for treating various forms of alopecia due to its vasodilatory effects. While topical minoxidil has been the standard treatment, low-dose oral minoxidil (LDOM) is emerging as an effective alternative. This study investigates LDOM's potential hypotensive effects., Methods: Studies were selected based on criteria such as the use of LDOM (≤5 mg/day) and reporting on blood pressure changes. Mean differences (MDs) were calculated for mean arterial pressure (MAP), systolic blood pressure, diastolic blood pressure, and heart rate., Results: LDOM did not significantly alter systolic blood pressure (MD: -0.13, 95% CI: -2.67-2.41) or diastolic blood pressure (MD: -1.25, 95% CI: -3.21-0.71). Though MAP was not significantly altered, there was a strong tendency toward decreased MAP (MD: -1.92, 95% CI: -4.00-0.17). There was a significant increase in heart rate (MD: 2.67, 95% CI: 0.34-5.01). Hypotensive symptoms were reported in 119 patients (5.0%), but no hypotensive episodes were observed. Hypertrichosis was the most frequent side effect, leading to 34.6% of discontinuations., Limitations: Studies lacked control groups and showed variability in dosing regimens and blood pressure monitoring., Conclusion: LDOM appears to be a safe treatment for alopecia with no significant impact on blood pressure., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Lippia alba (erva-cidreira) is often mentioned in Brazilian ethnopharmacological studies. Although its leaves have been used to treat hypertension, few studies have evaluated its hypotensive effects. This work aimed to evaluate the haemodynamic effects of Lippia alba methanolic extract and to characterise its chemical composition. Normotensive rats received an intravenous injection of L. alba extract. Systolic, diastolic, mean arterial pressures, and electrocardiographic data were analysed. 1 H-qNMR and LC-MS were used to assess the chemical composition. L. alba extract had significant hypotensive effects on systolic, diastolic, and mean arterial pressure. Acteoside was identified as major compound (292.6 ± 2.7 mg/g). Sixty-one other compounds were tentatively identified, mainly phenylethanoids, flavonoids, and iridoids. L. alba extract reduces systolic, diastolic, mean arterial pressure, and appears to be associated with a reduction in heart rate. Acteoside, a known hypotensive compound, may be responsible for these effects, but other structurally similar minority compounds may also contribute.

Background: controlled (deliberate/induced) hypotension is a technique by which the arterial blood pressure is lowered in a controllable manner to reduce surgical blood loss and improve the operative field visibility. There are pharmacological and nonpharmacological techniques for inducing hypotension. The nonpharmacological methods for deliberate hypotension include positioning and positive pressure ventilation to control venous return. Aim of the Work: to evaluate the efficacy of dexmedetomidine (DEX) as a hypotensive agent in comparison to nitroglycerin (NTG) in FESS regarding the bloodless field, reduction of mean arterial blood pressure, decrease inhalational anesthetic requirements (MAC), decrease perioperative opioid requirements, increase the time to first postoperative analgesic request and recovery profile and increase hemodynamics stability. Patients and Methods: we conducted this study on 20 patients who were planned to perform functional endoscopic sinus surgery and were randomly distributed into 2 equal groups: 10 patients received dexamedotomidine and equal number of patients received nitroglycerine. Serial measurements of mean arterial blood pressure and heart rate were obtained and records between both groups were compared. Results: There were statistically significant differences between both groups regarding heart rate as mean values of heart rate were lower among dexamedotomidine group. There were no statistically significant differences between both groups regarding mean arterial blood pressure values at different time points during the operation. Regarding the period after stopping infusion, mean values of heart rate and blood pressure were lower among dexamedotomidine group than nitroglycerine group after 5 minutes and after 10 minutes and the differences had statistically significant differences. Regarding postoperative period, both groups were comparable regarding heart rate and blood pressure immediately postoperative. Conclusion: From the results of this study, we could conclude that both Dexmedetomidine and Nitroglycerin can be effectively used in induced hypotensive anesthesia for ENT surgery as FESS. Both groups were comparable with intra operative MAP with no statistically significant differences. This study also show that Dexmedetomidine has added advantages as better haemodynamic stability than Nitroglycerin (No rebound HTN, no tachycardia). Has sedative and analgesic effect, reduce requirement of anesthetic agents and perioperative analgesia. Postoperative recovery score (Time to reach modified Aldert score more than nine significantly higher. Postoperative complication as nausea and vomiting is less. [ABSTRACT FROM AUTHOR]

Glaucoma is a group of chronic irreversible neuropathies that affect the retina and the optic nerve. It is considered one of the leading causes of blindness in the world. Although it can be due to various causes, the most important modifiable risk factor is the elevated intraocular pressure (IOP). In this case, the treatment of choice consists of instilling antihypertensive formulations on the ocular surface. The chronicity of the pathology, together with the low bioavailability of the drugs that are applied on the ocular surface, make it necessary to instill the formulations very frequently, which is associated, in many cases, with the appearance of dry eye disease (DED). The objective of this work is the design of topical ocular formulations capable of treating glaucoma and, at the same time, preventing DED. For this, two liposome formulations, loaded with brimonidine or with travoprost, were Tadeveloped using synthetic phospholipids and enriched by the addition of compounds with osmoprotective activity. The proposed formulations not only presented physicochemical characteristics (size, pH, osmolarity, surface tension, and viscosity) and encapsulation efficiency values (EE% of 24.78% and ≥99.01% for brimonidine and travoprost, respectively) suitable for ocular surface administration, but also showed good tolerance in human corneal and conjunctival cell cultures, as well as an in vitro osmoprotective activity. The hypotensive effect of both liposomal formulations was evaluated in normotensive albino New Zealand rabbits, showing a faster and longer lasting reduction of intraocular pressure in comparison to the corresponding commercialized products used as control. According to these results, the hypotensive liposomal formulations combined with osmoprotective agents would result in a very promising platform for the treatment of glaucoma and the simultaneous protection of the ocular surface. [ABSTRACT FROM AUTHOR]

In this study, a novel peptide, AEYLCEAC with high angiotensin-I-converting enzyme inhibitory (ACEI) activity was screened from oyster (Crassostrea gigas) hydrolysates, which was obtained from simulated gastro-intestinal digestion. Candidate peptides were confirmed to have a higher binding to angiotensin-I-converting enzyme (ACE) than the positive drug phosphoinic tripeptide calculated by Discovery Studio, and AEYLCEAC showed the highest ACE inhibition rate in vitro with a IC50 of 4.287 mM. Lineweaver-Burk plots confirmed that the peptidic inhibitory type of ACE is competitive. The molecular docking showed that ACEI activity of the AEYLCEAC was mainly due to the hydrogen bonding interactions with the active pockets (S1 and S2) of ACE. In vivo, AEYLCEAC effectively reduced diastolic blood pressure (DBP) and Systolic blood pressure (SBP) in hypertensive rats. These results indicate that AEYLCEAC might act as a helpful ingredient in functional foods or pharmaceuticals for the prevention and treatment of hypertension.

Introduction: Oxidative stress is involved in many diseases, including hypertension, kidney failure, and heart disease. This study aimed to evaluate the effect of hydroalcoholic Cichorium intybus extract on blood pressure in rats. Antioxidant activity, phenolic and flavonoid contents of the plant extract were also evaluated. Methods: In this study, 32 male Wistar rats weighing 250-300 g were divided into four groups of eight each. Animals in the control group were administered with normal saline and in the C. intybus groups with extract at 25, 50, and 100 mg/kg for two weeks. Then, the homodynamic parameters were examined by the Power lab. The phenolic and flavonoid contents were also evaluated by a spectrophotometer and the rate of free radical scavenging activity was measured by the diphenyl-1-picyryl-hydrazyl (DPPH) free radical method. Results: The free radical scavenging activity of C. intybus extract was obtained 47.85% of DPPH, and flavonoid and phenolic contents were 8.21 and 27.19 mg/g of dry extract, respectively. Meanwhile, median (MAP), systolic (SAP) and diastolic arterial pressure (DAP) significantly decreased in the 50 mg/kg extract-treated group compared to the control and 200 mg/kg extract-treated groups. Conclusion: Ethanol extract of C. intybus plays a protective role against hypertension, which, in part, might be due to antioxidant compounds of the plant against free radicals.

Abstract Introduction Desmodium canum (Strong Back) is deemed a versatile traditional medicine, where it is used to treat diabetes, hypertension, asthma and erectile dysfunction. Aim To identify the various phytochemicals present within extracts of D. canum, their antioxidant capabilities and their effects on blood glucose levels, haemodynamic parameters and testosterone levels in healthy Sprague-Dawley (S-D) rats. Method Crude extracts were obtained using hexane, ethyl acetate and methanol. These were analysed for various phytochemicals and their antioxidant potential assessed using the 2,2-diphenyl-1picrylhydrazyl (DPPH) method. The extracts were investigated for hypoglycaemic potential using the Oral Glucose Tolerance Test (OGTT), where extracts were administered intravenously (50 mg/kg BW) to fasted rats and their blood glucose readings monitored at 30 min intervals. The hypotensive effect of the extracts were also investigated where rats were administered intravenously at 50 mg/kg BW. These haemodynamic parameters were monitored using the CODA 6 machine at 5 min intervals for a total of 20 min. Additionally, the effect on testosterone level was investigated in male rats where extracts were administered daily by oral gavage. Serum testosterone levels were then determined using an ELISA kit. Results The different extracts showed varying phytochemical and pharmacological properties. The methanol extract showed antioxidant capabilities, while the ethyl acetate extract showed significant hypoglycaemic and hypotensive effects when compared with the control. The hexane extract showed significant activity in increasing the testosterone when compared with the control. Conclusion D. canum extracts showed significant pharmacological activities in normal Sprague- Dawley rats.

Background: Obtaining intravenous access in hypotensive patients is challenging and may critically delay resuscitation. The Graduated Vascular Access for Hypotensive Patient (GAHP) protocol leverages intraosseous fluid boluses to specifically dilate proximal veins. This study aims to evaluate the efficacy of GAHP in maximizing venous targets through early distal intraosseous access and a small fluid bolus., Methods: This was a prospective randomized cadaveric pilot study to evaluate extremity venous engorgement during intraosseous infusion. Cadavers (n = 23) had an intraosseous needle inserted into four sites: distal radius, proximal humerus, distal femur, and distal tibia. Intraosseous saline was rapidly infused, venous optimization was measured using real-time ultrasound. Primary outcome was maximum vessel circumference increase with intraosseous infusion. Secondary outcomes were: time to maximum circumference, and infusion volume required. Statistical analyses included Levene's test for equality of variances, Wilcoxon signed-rank test, and generalized estimating equation., Results: There was a significant mean increase of 1.03 cm (95% CI 0.86, 1.20), representing a difference of 102%. We found no significant difference in time to optimize vessel circumference across sites, but volume required significantly differed., Conclusion: GAHP quickly and effectively increased the circumference of anatomically adjacent veins. Anatomical sites did not differ on time to reach maximum enlargement of vessels following intraosseous infusion but did differ in terms of volume required to maximize vessel circumference. Further research is needed using live, hypotensive patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024 Published by Elsevier B.V.)

Purpose: Traumatic abdominal injury is associated with significant mortality, especially in hemodynamically unstable patients. Trauma management now supports more conservative surgical management with judicious non-operative management. The aim of this study is to use STAG data to characterize abdominal trauma outcomes, focusing on factors that may influence mortality. Methods: A retrospective analysis of prospectively collected STAG data was queried using AIS codes for Scottish abdominal trauma patients between 2011 and 2015. Patients were divided into non-survivor and survivor groups, reflecting mortality. Following this, outcomes and injury patterns of patients undergoing operative or non-operative management were compared between groups. Results: A total of 1226 were analyzed. The mean age of the cohort was 42.47 ± 19.42 years, with most patients suffering blunt injuries. Non-survivors had more severe injuries to the liver, diaphragm, pancreas, vasculature, and pelvis (p < 0.001, p = 0.005, p = 0.025, p < 0.001, and p < 0.001, respectively). Survivors more often received CT scanning (0.09 [0.03–0.27]) and underwent surgical intervention (57.4% vs 39.7%; p = 0.001). Non-survivors more often had a shorter time till operative intervention (2.6 h vs 6.3 h, p < 0.001). Conclusions: About 7% of patients in the STAG registry display abdominal injury. Mortality was found to have strong associations with older age, hemodynamic instability, poor neurological status, and head and neck injury. Outcomes may improve with the anticipated creation of the Scottish Trauma System. [ABSTRACT FROM AUTHOR]

Securidaca longipedunculata, Olax subscorpioidea and Persea americana are medicinal plants that serves several purposes in treating many ailments. In this study, the cardiovascular activity of ethanolic extract of the plants were separately assessed using rats of average weight of 181g. 20 Rats were utilized for each plant. Cardiovascular parameters were recorded through cannulation of the carotid artery on anaesthetized normotensive rats, following intravenous administration of ethanolic extract of S. longepedunculata (50-200mg kg-1), O. subscorpioidea (12.5 -50mg kg-1) and P. americana (200 and 400mg kg-1). Acetylcholine and nifedipine served as reference drugs while 0.9% saline was control. After administration of the extracts, physiological reaction of the animals were recorded via a polygraph device fastened to a pressure transducer. Extract caused significant (p˂0.05) decreased pulse rate, mean arterial, systolic and diastolic blood pressure. These extracts elicited significant blood pressure variation patterns that suggested an increased hypotensive activities. This may be adduced to the likely presence of some phytochemicals such as flavonoids in the plants that could possibly act as vasodilators or inhibitors of angiotensin converting enzymes. It may likely act like calcium channel blockers, β-blockers or natriuretic peptides. This pharmacological investigation therefore gives credence and justification to the ethnomedical, anecdotal and folkloric uses of S. longepedunculata, O. subscorpioidea and P. americana as blood depressants and revealed that O. subscorpioidea is more potent followed by S. longepedunculata and P. americana being the least potent.

Hypertension is one of the most prevalent cardiovascular risks and an important cause of morbidity and mortality across the world. Since antioxidant phytochemicals can regulate the renin-angiotensin system and lower blood pressure, F. benghalensis stem bark extract (FBE) rich in polyphenols was investigated for its ability to regulate blood pressure in normotensive and angiotensin II-induced hypertensive rats. Rats were divided into four groups namely, control (saline injection), FBE (extract alone, 10 mg/kg), Ang II (Ang II alone, 0.5 µg/kg), and Ang II + FBE (Ang II + extract, 10 mg/kg). All of the treatments were administered through the intravenous route and in Ang II + FBE group, Ang II was injected 30 min after injection of the extract. Hemodynamic parameters namely, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), and heart rate (HR) were recorded by the BIOPAC system after cannulation of the carotid artery and jugular vein. FBE reduced SBP, DBP, MABP, and HR to varying degrees in normotensive rats compared to the control group. In the case of angiotensin II-induced hypertension, FBE administration resulted in a significant decrease in SBP, DBP, and MABP compared to the Ang II group. SBP, DBP, and MABP were decreased to an extent of 27, 30, and 29%, respectively by FBE. It is noteworthy that FBE reduced SBP, DBP, and MABP to baseline levels suggesting significant hypotensive/antihypertensive activity. It is concluded that the antihypertensive action of F. benghalensis extract is due to the presence of phenolic compounds. [ABSTRACT FROM AUTHOR]

Glaucoma is a group of chronic irreversible neuropathies that affect the retina and the optic nerve. It is considered one of the leading causes of blindness in the world. Although it can be due to various causes, the most important modifiable risk factor is the elevated intraocular pressure (IOP). In this case, the treatment of choice consists of instilling antihypertensive formulations on the ocular surface. The chronicity of the pathology, together with the low bioavailability of the drugs that are applied on the ocular surface, make it necessary to instill the formulations very frequently, which is associated, in many cases, with the appearance of dry eye disease (DED). The objective of this work is the design of topical ocular formulations capable of treating glaucoma and, at the same time, preventing DED. For this, two liposome formulations, loaded with brimonidine or with travoprost, were Tadeveloped using synthetic phospholipids and enriched by the addition of compounds with osmoprotective activity. The proposed formulations not only presented physicochemical characteristics (size, pH, osmolarity, surface tension, and viscosity) and encapsulation efficiency values (EE% of 24.78% and ≥99.01% for brimonidine and travoprost, respectively) suitable for ocular surface administration, but also showed good tolerance in human corneal and conjunctival cell cultures, as well as an in vitro osmoprotective activity. The hypotensive effect of both liposomal formulations was evaluated in normotensive albino New Zealand rabbits, showing a faster and longer lasting reduction of intraocular pressure in comparison to the corresponding commercialized products used as control. According to these results, the hypotensive liposomal formulations combined with osmoprotective agents would result in a very promising platform for the treatment of glaucoma and the simultaneous protection of the ocular surface.

The modern trend of research is highly focused on finding new bioactive molecules from medicinal plants. As a functional bicyclic monoterpene, Bornyl acetate (BA) has displayed antioxidant and anti-inflammatory properties in different types of cells and tissues. The purpose of this research was to evaluate the probable hypotensive effect of BA, an underlying mechanism(s) backboned by in-silico studies. Mean arterial pressure and heart rate were recorded via invasive blood pressure measuring technique in normotensive Sprague-Dawley rats following the administration of BA (1-80mg/kg). Docking studies were carried out with various targets involved in the pathophysiology of hypertension.RO5 and ADMET properties were also evaluated. In the current study dose-dependent reduction in systolic, diastolic and mean arterial pressure was observed. Pretreatment with atropine and captopril significantly (p<0.001) reduced the hypotensive effect produced by BA. On the other hand docking studies showed pronounced interactions with M2 mAch receptor in an agonistic way and ACE protein in an antagonistic way. BA justified all cut-off limits of RO5 and had an acceptable predicted computational toxicity profile. Results postulate that dose-dependent hypotensive effect of BA is mediated through the muscarinic pathway and ACE inhibitory activity corresponding well with findings of in-silico studies. [ABSTRACT FROM AUTHOR]

A 60 year old male patient reported to the OPD with the complaint of pain in lower left first mandibular molar for 3 days. The pain was continuous, dull and radiated to the ipsilateral jaw and ear, it aggravated on chewing and was relieved by analgesics. He was a known diabetic and hypotensive and was on medication. Patient was habitual of betel quid and smoking since a long time. Past dental history showed a partial denture on lower anteriors.

Abstract Purpose: To establish a hypotensive brain death pig model and observe the effects of hypotension on small bowel donors. Methods: The hypotensive brain death model was produced using the modified intracranial water sac inflation method in ten domestic crossbred pigs. Effects of hypotensive brain death on small bowel tissue morphology were evaluated through changes in intestinal tissue pathology, tight junction protein of the intestinal mucosa and plasma intestinal fatty acid-binding protein (i-FABP) levels. The pathophysiological mechanism was examined based on changes in superior mesenteric artery (SMA) blood flow and systemic hemodynamics. Results: After model establishment, SMA blood flow, and the mean arterial pressure (MAP) significantly decreased, while heart rate increased rapidly and fluctuated significantly. Small bowel tissue morphology and levels of tight junction protein of the intestinal mucosa showed that after model establishment, small bowel tissue injury was gradually aggravated over time (P

The worldwide burden of hypertension and its associated cardiovascular diseases have urged researchers to explore for alternative therapies. Together with laboratory studies, field surveys on the documentation of traditional antihypertensive therapies have expanded across the world. However, a compilation and analysis of these field studies has not been done so far. This review aim to document all traditional medicinal plants used globally for the management of hypertension. Field studies were retrieved from main databases including Sciencedirect, Medline/PubMed, and Google Scholar. 433 surveys were obtained which dated from 1970 to 2019. A total of 1329 traditionally used plant species (823 genera and 176 families) were reported across 90 countries against hypertension. Compositae (Genera: 68; Species:103) and Lamiaceae (Genera:39; Species:103) were the families with the most used species. The main species (in order of number of reports) were Allium sativum L., followed by Olea europaea L., Allium cepa L., Annona muricata L., Persea americana Mill., Citrus aurantiifolia (Christm.) Swingle, Catharanthus roseus (L.) G.Don, Moringa oleifera Lam., Cymbopogon citratus (DC.) Stapf, and Carica papaya L. Pakistan (Family:81; Species:246) reported the highest number of plant species followed by Mexico, Nigeria, India, Algeria, Morocco, Thailand, Suriname, Benin, and Iran. Leaf (35%), fruit (12%), and root (10%) were the most preferred plant parts while the main methods of preparation were decoction (50%) and infusion (22%). This study is the first of its kind to compile all traditionally used hypotensive medicinal plants across the world. It is recommended that another systematic review be conducted on the biological properties of all identified species in our review to identify those which have been scientifically validated in in vitro, in vivo , and clinical studies before they can be considered as alternative or complementary antihypertensive therapies. Image, graphical abstract • A comprehensive compilation of medicinal plants used globally for hypertension is reported. • 433 surveys were reviewed, with 1329 species from 823 genera and 176 families reported across 92 countries. • Compositae and Lamiaceae (103 Species) were the main families. • Validation of such traditional botanical remedies is recommended. [ABSTRACT FROM AUTHOR]

Introduction: Desmodium canum (Strong Back) is deemed a versatile traditional medicine, where it is used to treat diabetes, hypertension, asthma and erectile dysfunction. Aim: To identify the various phytochemicals present within extracts of D. canum, their antioxidant capabilities and their effects on blood glucose levels, haemodynamic parameters and testosterone levels in healthy Sprague-Dawley (S-D) rats. Method: Crude extracts were obtained using hexane, ethyl acetate and methanol. These were analysed for various phytochemicals and their antioxidant potential assessed using the 2,2-diphenyl-1picrylhydrazyl (DPPH) method. The extracts were investigated for hypoglycaemic potential using the Oral Glucose Tolerance Test (OGTT), where extracts were administered intravenously (50 mg/kg BW) to fasted rats and their blood glucose readings monitored at 30 min intervals. The hypotensive effect of the extracts were also investigated where rats were administered intravenously at 50 mg/kg BW. These haemodynamic parameters were monitored using the CODA 6 machine at 5 min intervals for a total of 20 min. Additionally, the effect on testosterone level was investigated in male rats where extracts were administered daily by oral gavage. Serum testosterone levels were then determined using an ELISA kit. Results: The different extracts showed varying phytochemical and pharmacological properties. The methanol extract showed antioxidant capabilities, while the ethyl acetate extract showed significant hypoglycaemic and hypotensive effects when compared with the control. The hexane extract showed significant activity in increasing the testosterone when compared with the control. Conclusion: D. canum extracts showed significant pharmacological activities in normal Sprague- Dawley rats. [ABSTRACT FROM AUTHOR]

Teucrium stocksianum Boiss. is an aromatic perennial herb. It has long been used traditionally in the treatment of hypertension in northern areas of Pakistan. The aim of this study was to evaluate its folkloric claim as hypotensive plant, phytochemical analysis and to predict potential phytoconstituent through in-silico studies. Hypotensive effect was investigated in anesthetized normotensive Sprague-Dawley rats. Recording of chronotropic and inotropic effect of plant extract in isolated right atria was done using tissue organ bath technique. Further, phytochemical characterization was performed through LC-MS. Whereas docking studies were carried out against M2 mAchR and Ca2+ Channel receptor. Dose dependent reduction in systolic, diastolic, mean arterial pressure and heart rate was observed. Pretreatment with atropine and amlodipine significantly (p<0.001) reduced the hypotensive and negative chronotropic and inotropic effect. Phytochemical studies revealed the presence of twenty active compounds including Luteolin, Sarmentosin epoxide and Quinic acid. Docking studies showed pronounced interactions of majority of these phytochemicals with M2 mAch receptor in agonistic way and Ca2+ Channel receptor in antagonistic way. Results speculate that dose dependent hypotensive and bradycardia effect of Teucrium stocksianum are mediated through muscarinic pathway and Ca2+antagonism and is also well predicted by in-silico studies. [ABSTRACT FROM AUTHOR]

Indigofera argentea is widely used for the management of gastrointestinal, respiratory and cardiac disorders. This study was done to explore scientific basis of its uses. Aqueous methanolic extract of Indigofera argentea and its fractions were studied on isolated tissues of rabbit's jejunum, trachea, aorta and atrium. Castor oil induced diarrheal model was used for the study of the antidiarrheal effect and pre-anesthetized rats were used for hypotensive study. Concentration dependent spasmolytic effect of the extract upon isolated jejunum, trachea and aorta was observed. Concentration response curves constructed upon isolated rabbit jejunum, revealed the presence of calcium channel blocker in the plant extract. Moreover, significant reduction (P<0.05) in atrial force of contraction but non-significant reduction in rate of contraction was seen by the application of plant extract. Protection (P<0.05) against diarrhea was observed by the administration of crude extract to rats which were pretreated with castor oil. When given to rats intravenously, the extract showed hypotensive effect. Experimental findings justified the traditional uses of Indigofera argentea on pharmacological basis for the management of disorders pertaining to gut, airway and hypertensive situation. [ABSTRACT FROM AUTHOR]

The aerial part of Biebersteinia heterostemon Maxim. (Geraniaceae Biebersteiniaceae) known as ming jian na bao in Chinese, has been traditionally used in Tibetan folk medicine for treatment of diabetes and hypertension. The aim of the present study was to evaluate the effects of galegine obtained from an ethanol extract of the entire Biebersteinia heterostemon plant on the rat’s cardiovascular system in order to characterize its contributions as an antihypertensive agent. The antihypertensive effect of galegine was investigated in pentobarbital-anesthetized hypertensive rats at three dose levels based on the LD50 of galegine. Meanwhile a positive control group received dimaprit with the same procedure. Dimaprit infusion induced a significant hypotension which declined by an average margin of 20%. Simultaneously, single administration of galegine at the doses of 2.5, 5, and 10 mg/kg by intraperitoneal injection induced an immediate and dose-dependent decrease in mean arterial blood pressure (MABP) by an average margin of 40% with a rapid increase in heart rate (HR). We demonstrated that galegine is effective in reducing blood pressure in anesthetized hypertensive rats with rapid onset and a dose-related duration of the effects. The results indicate that galegine was the bioactive compound which can be used as a pharmacophore to design new hypertensive agents.

Context: Fructus Psoralea, Psoralea corylifolia L. (Leguminosae), has been widely used in traditional medicines for the treatment of dermatitis, leukoderma, asthma and osteoporosis. Objectives: In this study, we sought to study mechanisms underlying the vasoactive properties of Psoralea corylifolia extract (PCE) and its active ingredients. Materials and methods: To study mechanisms underlying the vasoactive properties of PCE prepared by extracting dried seeds of Psoralea corylifolia with 70% ethanol, isometric tension recordings of rat aortic rings and the ionic currents through TRPC3 (transient receptor potential canonical 3) channels were measured with the cumulative concentration (10–600 μg/mL) of PCE or its constituents. Results: Cumulative treatment with PCE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC50 values of 61.27 ± 3.11 and 211.13 ± 18.74 μg/mL, respectively. Pretreatment with inhibitors of nitric oxide (NO) synthase, guanylate cyclase, or cyclooxygenase and pyrazole 3, a selective TRPC3 channel blocker, significantly decreased PCE-induced vasorelaxation (p

Brewer's spent grain (BSG) is a co-product of the brewing industry and is a potentially rich source of bioactive peptides. A BSG protein hydrolysate, manufactured at a semi-pilot scale, mediated significant hypotensive effects 6 h after ingestion in spontaneously hypertensive rats. This hydrolysate was fractionated and further analysed by UPLC-ESI-MS/MS for peptide identification. The peptides, IPY and LPY demonstrated the highest antioxidant activity (0.37 ± 0.02 and 0.34 ± 0.02 µmol Trolox equivalents µM peptide−1, respectively), IPLQP and LPLQP had the highest ACE inhibitory activity (IC50: 3.10 ± 0.60 and 3.17 ± 0.60 µM, respectively) while IPVP had the highest DPP-IV inhibitory activity (IC50: 38.67 ± 5.94 µM). Overall, peptides containing I had higher in vitro bioactivities when compared to peptides having L. Novel BSG peptides were identified with potential for application as naturally derived ingredients for the management of cardiovascular disease and type 2 diabetes.

The objective of this study was to evaluate the in vitro anti-oxidant, hypo-tensive and the diuretic activities of Origanum glandulosum leaves in rat. Chemical analysis revealed the isolation of katuranin and 5-isopropyl-3-methylphenol. Ethyl acetate extract possessed highest scavenging activity against DPPH and hydroxyl radicals. Intravenous administration of extracts (0.04 to 12 mg/kg body weight) dose-dependently decreased the blood pressure (systolic, diastolic and mean) of the anesthetized rat. Methanol extract showed dose-dependent diuretic activity by increasing the urine output (77%) and the urinary excretion of sodium and potassium. In conclusion, this study supports the use of O. glansulosum in traditional medicine as hypotensive and diuretic agents.

Background: Plant products derived from natural sources have been used in medicine as a raw material and newer kinds of drug molecules in pharmaceuticals and other allied health sectors. Phytochemicals have numerous medicinal potentials, including anti- ageing, anti-carcinogenic, anti-microbial, anti-oxidant, and anti-inflammatory activity in medicine. Development and biological application of herbal products in modern medicine signified the value of traditional medicinal plants in health care systems., Methods: The objective of the present study was to explore the scientific knowledge of the medicinal importance and therapeutic potential of artemetin in medicine. However, scientific investigations for their pharmacological activities in medicine have been done through scientific data analysis of different scientific research work collected from PubMed, Google, Science Direct and Google Scholar in order to know the biological importance of artemetin in medicine. Moreover, analytical data of artemetin have also been discussed in the present work., Results: The present work scientific data signified the biological potential of artemetin in medicine. Artemetin has been derived from numerous medicinal plants and dietary herbs, including Artemisia absinthium, Artemisia argyi, Achillea millefolium, and Vitex trifolia . Artemetin has anti-malarial, anti-oxidant, anti-apoptotic, anti-microbial, anti-tumoral, antiatherosclerotic, anti-inflammatory, hypotensive and hepatoprotective effects. Further, the biological role of artemetin on lipid oxidation, cytokine production, lipoxygenase, and estrogen- like effects was also investigated in the present work. Analytical data on artemetin in the present paper signified their important role in the isolation, separation, and identification of different classes of pure phytochemicals, including artemetin in medicine., Conclusion: Scientific data analysis of artemetin signified its therapeutic potential in medicine for the development of newer scientific approaches for different human disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study is part of a research project in Urban Ethnobotany, which studies the botanical knowledge in urban areas. It includes 83 medicinal plants marketed as hypotensive in the Metropolitan Area of Buenos Aires. Data on the local use of these plants were gathered via field work and qualitative ethnobotanical methodologies. The 180 outlets surveyed consisted of: 145 stores of the general commercial circuit (pharmacies, herbalists, dietetics) and 35 outlets of the restricted commercial circuits of two immigrants segments, Chinese and Bolivians. The "Bolivian Market" of the Liniers district included 30 outlets (local and street stalls). The so-called "Chinatown", a sector of the Belgrano neighborhood, included five large supermarkets. A search of academic studies related to hypertension was carried out to correlate the assigned plant use. Of the 83 species surveyed, 10 (12%) are invisible to most of the local urban population, while the remaining 73 (88%) are visible. Ethnobotanical information is provided on plants linked to hypertension treatment and on its scientific validity, adapting it to consumers who decide to use these plants. [ABSTRACT FROM AUTHOR]

Although leaves of Anchietea salutaris are used in Brazilian traditional medicine, there is no available data in the literature proving its efficacy and safety. Thus, the aim of the study was to perform a meticulous botanical, phytochemical, toxicological, and pharmacological investigation of A. salutaris in Wistar rats. At first, a morphoanatomical characterization of Anchietea pyrifolia leaves and stems was performed. Then, a purified infusion (ethanol-soluble fraction obtained from A. pyrifolia [ESAP]) was obtained followed by its chemical profile elucidation. Furthermore, an acute toxicity test was performed, and the acute and prolonged diuretic and hypotensive effects were also evaluated in Wistar rats. Finally, the vasodilatory responses of ESAP in mesenteric vascular beds were investigated. The main secondary metabolites identified from ESAP were O-glycosylated flavonoids, chlorogenic acids, and phenylpropanoic acid derivatives. ESAP did not promote any toxic effects in female rats nor increased urinary excretion in male rats after a single exposure. However, ESAP significantly reduced renal elimination of sodium, potassium, and chloride after prolonged treatment. An ESAP highest dose promoted significant acute hypotension without affecting blood pressure levels after prolonged use. Furthermore, its cardiovascular effects seem to be related with the calcium-activated potassium channel activation in resistance vessels. [ABSTRACT FROM AUTHOR]

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Anogeissus acuminata (Roxb. ex DC.) is a folkloric medicinal plant in Asia; including Pakistan; used as a traditional remedy for cardiovascular disorders. This study was planned to establish a pharmacological basis for the trivial uses of Anogeissus acuminata in certain medical conditions related to cardiovascular systems and to explore the underlying mechanisms. Mechanistic studies suggested that crude extract of Anogeissus acuminata (Aa.Cr) produced in vitro cardio-relaxant and vasorelaxant effects in isolated paired atria and aorta coupled with in vivo decrease in blood pressure by invasive method; using pressure and force transducers connected to Power Lab Data Acquisition System. Moreover; Aa.Cr showed positive effects in left ventricular hypertrophy in Sprague Dawley rats observed hemodynamically by a decrease in cardiac cell size and fibrosis; along with absence of inflammatory cells; coupled with reduced levels of angiotensin converting enzyme (ACE) and renin concentration along with increased concentrations of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In Acute Myocardial Infarction (AMI) model; creatine kinase (CK), creatine kinase-MB (CK-MB) and lactic acid dehydrogenase (LDH levels) were found to be decreased; along with decreased necrosis; edema and recruitment of inflammatory cells histologically. In vivo and ex vivo studies of Anogeissus acuminata provided evidence of vasorelaxant; hypotensive and cardioprotective properties facilitated through blockage of voltage-gated Ca++ ion channel; validating its use in cardiovascular diseases

Talisia esculenta (A. St.-Hil.) Radlk. is a large tree belonging to family Sapindaceae and popularly known as "pitombeira" or "pitomba." Although species have relevant economic and medicinal uses in Brazil, no study has investigated its effectiveness as a diuretic, hypotensive, and antihypertensive agent. The aim of this study was to present a detailed anatomical and histochemical study for T. esculenta and provide important safety and efficacy parameters. After morpho-anatomical and microchemical study, a purified aqueous extract (ethanol soluble fraction obtained from T. esculenta [ESTE]) was obtained, and detailed phytochemical investigation was performed. Subsequently, acute oral toxicity test was performed in male and female rats. Moreover, diuretic, hypotensive, and antihypertensive effects on normotensive and spontaneously hypertensive rats (SHR) were investigated. Finally, the effects of prolonged treatment with ESTE on serum levels of nitrite, thiobarbituric acid reactive species, and nitrotyrosine were also measured in SHR. Oral treatment with ESTE did not induce acute toxic effects and did not affect urine production, blood pressure, or heart rate of normotensive and SHR. Prolonged treatment with ESTE was able to increase serum nitrite levels and significantly reduce oxidative and nitrosative stress markers in SHR. Data obtained showed that ESTE has a significant antioxidant activity without showing any clinical signs of acute toxicity. The use of this species as a diuretic, hypotensive, or antihypertensive agent should be carried out with caution, since administration in rodents did not produce renal and/or hemodynamic responses that justify this indication. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Luehea divaricata Mart. (Malvaceae) is an important medicinal species that is widely used as a diuretic in the Brazilian Pantanal region. An ethanolic supernatant that was obtained from an infusion of leaves of this species (ESLD) was recently shown to exert hypotensive and diuretic activity. Nevertheless, the secondary metabolites that are responsible for this activity and the molecular mechanisms of pharmacological action remain unknown. Aim We performed a detailed study to identify possible active metabolites that are present in different ESLD fractions and investigated their effects on renal and peripheral arteriolar tone. We further evaluated their interrelations with sustained diuretic and hypotensive actions. Materials and methods The ESLD was first obtained from L. divaricata leaves, and liquid-liquid fractionation was performed. The fractions were analyzed by liquid chromatography-mass spectrometry. An ethyl acetate fraction (AceFr), n -butanolic fraction (ButFr), and aqueous fraction (AqueFr) were then orally administered in male Wistar rats in a single dose or daily for 7 days. The doses were previously defined based on the yield that was obtained from each fraction. Hydrochlorothiazide was used as a positive control. Blood pressure, heart rate, urinary volume, pH, density, and urinary sodium, potassium, chloride, and calcium levels were measured. Serum levels of nitrite, thiobarbituric acid reactive species, nitrotyrosine, aldosterone, vasopressin, and plasma angiotensin converting enzyme activity were also measured. Finally, the direct effects of the ButFr on renal and mesenteric arteriolar tone and the role of nitric oxide and prostaglandins in the renal and hemodynamic effects were investigated. Results Of the fractions that were tested, only the ButFr exerted significant diuretic and saluretic effects. The AceFr and ButFr also had acute hypotensive effects, but only the ButFr maintained its response after 7 days of treatment. Prolonged treatment with the ButFr increased serum nitrite levels and significantly reduced oxidative and nitrosative markers of stress. Additionally, the ButFr caused a vasodilatory response in the renal and mesenteric arteriolar beds through the release of nitric oxide and prostaglandins. Finally, the diuretic and hypotensive effects of the ButFr were completely blocked by pretreatment with N ω-nitro- L -arginine methyl ester and indomethacin, thus demonstrating the direct involvement of nitric oxide and prostaglandins in these effects. Conclusion The ButFr that was obtained from Luehea divaricata exerted sustained diuretic and hypotensive effects. These effects were apparently attributable to the release of nitric oxide and prostaglandins, which reduce renal and peripheral arteriolar tone and lead to an increase in the glomerular filtration rate and a reduction of global peripheral resistance. These findings suggest that the ButFr may be a potential complementary therapy for several conditions in which diuretic and hypotensive effects are required. [ABSTRACT FROM AUTHOR]

The aim of this study was to quantitatively evaluate the efficacy of induced hypotensive anesthesia in decreasing facial soft tissue perfusion during orthognathic surgery using laser-assisted indocyanine green fluorescence angiography. This retrospective study involved the evaluation of 16 patients who underwent orthognathic surgery. Data collection included facial tissue perfusion of the bilateral cheeks and chin at normotension and with pharmacologically induced hypotensive anesthesia. There were statistically significant differences in the facial tissue perfusion at normal and depressed levels of blood pressure ( P < 0.001). This study used an objective measure to demonstrate the long-standing belief that hypotensive anesthesia is efficacious in reducing tissue perfusion in the surgical field. The data suggest that pharmacologically depressing the level of mean arterial pressure by 18% may result in a 41–52% decrease in facial soft tissue perfusion. This study reports a novel method of quantitative analysis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Although Luehea divaricata Mart. (Malvaceae) is popularly used by the population of the Brazilian Pantanal for the treatment of different types of kidney diseases, no study has been carried out to prove this ethnobotanical indication. Aim To investigate the possible cardiorenal effects of an herbal preparation obtained from L. divaricata leaves. Materials and methods First, to provide quality control standards, a detailed morphological and microchemical characterization of L. divaricata leaves was performed. Then, the purified aqueous extract was obtained from the leaves of this species (ESLD) and a thorough phytochemical characterization was performed. Subsequently, acute oral toxicity test was performed after single administration of different doses (5, 50, 300, 2000 mg/kg) in male and female Wistar rats. Finally, the diuretic, hypotensive and antioxidant properties of ESLD (30, 100, 300 mg/kg) were evaluated after acute and prolonged treatment and the role of angiotensin converting enzyme, aldosterone, vasopressin, and nitric oxide in these effects was investigated. Results Analyses performed by liquid chromatography–mass spectrometry showed that the main secondary metabolites present in ESLD were flavonol O-glycosides and flavone C-glycosides. Acute and prolonged treatment with ESLD was able to expressively increase urinary volume and electrolyte excretion. Mean blood pressure and systolic blood pressure were also significantly reduced after acute treatment. Moreover, treatment with ESLD was able to reduce thiobarbituric acid reactive species and increase serum nitrate levels. Conclusion The data obtained showed that ESLD has an important diuretic and hypotensive effect, which is probably dependent on the reduction of oxidative stress and increased bioavailability of nitric oxide. [ABSTRACT FROM AUTHOR]