Release Of Vasoactive Substances Research Articles

Ultrasound Percutaneous Tenotomy: An Intervention for Managing Lateral Epicondylitis: A Narrative Review

A growing emphasis is being focused on percutaneous ultrasonic tenotomy for expedited recovery from lateral epicondylitis (LE) and enhanced functionality. The TX1 tissue removal system, also known as the Tenex device from Tenex device (Tenex Health Inc., Lake Forest, CA, USA), notably excels in the management of chronic LE. Utilizing ultrasonic energy, this device offers three tips, namely, TX1, TX2, and TXBone-introducing novel avenues, for determining the previously inaccessible tendon pathology. The procedure disrupts degenerated segments, which creates fenestrations that induce local hemorrhage and the release of vasoactive substances. The overarching goal of Tenex is to boost vascularity through the initiation of tendon repair via the deposition of new collagen and elimination of necrotic tissues. This review assesses Tenex’s effectiveness though gathering information, aiming to understand how it helps doctors and other healthcare professionals in their work.

Abstract P3001: Regulation Of Perivascular Adipose Tissue By Follistatin In Hypertension

Follistatin lowers BP and improves resistance artery health in spontaneously hypertensive rats (SHR), a model of essential HTN. Functionally, follistatin improves smooth muscle contraction and endothelium-dependent relaxation. Structurally, increased medial collagen was inhibited. Vascular ROS were also reduced. Perivascular adipose tissue (PVAT) regulates vascular tone via release of vasoactive substances. Oxidative stress in PVAT, as in HTN, induces release of contractile agents. Transition from white to brown PVAT is associated with decreased risk of CVD. We analyze effects of follistatin on PVAT and its regulation of vessel function in SHR and normotensive Wistar Kyoto (WKY) rats. White and brown PVAT were dissected from treated rats; arteries were isolated from untreated donors. PVAT was introduced near strain-matched donor arteries and assessed for ROS levels and contractility using DHE and wire myography, respectively. In some vessels, endothelium was denuded to assess its contribution to contraction. Follistatin reduced ROS, hypercontractility, and improved relaxation in a PVAT-dependent manner. Brown PVAT induced significant anti-contractile and antioxidant effects. Elevated expression of adipose tissue browning markers and decreased adipocyte area with follistatin, support PVAT browning effects. Endothelium removal results in augmented vessel constriction, effects reduced by follistatin. Follistatin improves SHR smooth muscle tone in a PVAT-dependent manner, likely through the inhibition of vascular ROS and browning of PVAT. Future work will profile PVAT effects of follistatin through unbiased proteomic analysis. Although most vessels are surrounded by PVAT, studies of PVAT-vessel interaction in HTN are few. By characterizing PVAT dysfunction, we aim to outline specific PVAT-mediated pathways involved in lowering BP and improving vascular function and structure. Results will provide new insights into PVAT-targeted therapy for essential HTN, allowing potential translation of benefits to obesity and other diseases exhibiting PVAT dysfunction.

Patent foramen ovale in carcinoid heart disease: The potential role for and risks of percutaneous closure prior to cardiothoracic surgery.

Neuroendocrine tumours (NETs) are rare but once metastasised, can lead to the release of vasoactive substances into the systemic circulation, and the classical features of carcinoid syndrome (CS) such as flushing and diarrhoea. A consequence of CS is carcinoid heart disease (CHD) which primarily affects the right-sided heart valves and can eventually lead to right heart failure. In this cohort, tricuspid and/or pulmonary valve replacement provides symptomatic relief. A patent foramen ovale (PFO) in patients with CHD can lead to the shunting of oxygen deficient blood to the systemic circulation causing hypoxaemia and reduced exercise tolerance. Additionally, the haemodynamic changes caused by regurgitant right-sided heart valves can increase the patency of a PFO allowing the passage of vasoactive substances to the systemic circulation thereby affecting the left-sided heart valves. We present data on the incidence of PFO in patients referred for surgery at our centre, in which the standard approach is to close the defect at time of cardiothoracic surgery. In addition, we present a series of four cases that highlight how the option of percutaneous PFO closure prior to open valve surgery may reduce haemodynamic instability and open a window of opportunity to enhance preoperative status. Percutaneous PFO closure then acts as a bridge to definitive cardiothoracic surgery, although there are risks in such an approach.

Research progress in pathogenesis and traditional Chinese medicines treatment of ischemic stroke-related headache

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

#4808 DIFFERENTIATING POSTPARTUM HELLP SYNDROME FROM ATYPICAL HEMOLYTIC UREMIC SYNDROME

Abstract Background and Aims HELLP (hemolysis, elevated liver enzymes, low platelets) is a severe variant of preeclampsia whose pathogenesis remains unknown but likely involves abnormal placentation, endothelial dysfunction and release of vasoactive substances. Complement dysregulation is implicated in the pathogenesis of atypical hemolytic uremic syndrome (aHUS) and there is growing evidence to support its role in HELLP syndrome. Here we present a case of postpartum thrombotic microangiopathy (TMA) in the setting of HELLP syndrome. Method We present a case report. Ethics approval was obtained by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Results A 22 year old G1P1 Caucasian woman presents at 37 weeks gestation with abdominal pain and severe hypertension. Labs demonstrated TMA including hemoglobin 95, platelets 30, LDH 2597, and schistocytes. She had severe transaminitis with AST 1845 and ALT 830, and proteinuric acute kidney injury. She was diagnosed with HELLP syndrome and treated with anti-hypertensives and emergency Caesarean section. Unfortunately, the infant did not survive, and there was no placental abruption. Platelets recovered by day 5 postpartum, LDH by day 7. However, renal function worsened and by day 6 postpartum, she required hemodialysis. A renal biopsy revealed acute and chronic TMA. She did not have cortical necrosis. Further workup revealed normal C3, C4 and ADAMTS13 levels. Dialysis was stopped after two weeks. By 6 months, her renal function and proteinuria returned to normal. Complement function testing revealed negative complement factor H autoantibody, but elevated soluble C5b-9 (sC5b-9) level (0.42 mg/L, normal <0.3). Ex-vivo serum C5b-9 deposition on human microvascular endothelial cells was assessed both on resting (182%, normal <150%) and on ADP-activated endothelial cells (273%, normal <150%). This test was repeated 6 months postpartum when renal function had normalized, and results were persistently abnormal both on resting (215%, normal <150%) and on ADP-activated endothelial cells (282%, normal <150%). aHUS genetic testing was negative. Conclusion Results from Burwick et al suggest that this patient had a very high likelihood of clinical aHUS in association with HELLP syndrome (elevated LDH >1832 U/L and creatinine >1.9 mg/dL) [1]. Identifiable aHUS genetic mutations only occur in 50% of aHUS patients. Complement function testing is not routinely assessed for postpartum HELLP; however, the severity of her HELLP syndrome prompted further investigation (C5b-9 deposition testing). The persistence of increased C5b-9 deposition 6 months postpartum for this patient mimics the findings of patients who have confirmed aHUS [2]. Our patient's unique results suggest the patient may be at risk for recurrent TMA/aHUS in her lifetime, particularly if another pregnancy is being considered. Future research should explore which pregnancy associated TMA patients may benefit from anti-complement therapy.

Late-stage diagnosis of carcinoid heart disease due to lack of access to health care

Carcinoid syndrome (CS) is a unique constellation of symptoms caused by release of vasoactive substances from neuroendocrine tumors (Pandit et al., StatPearls, 2022). Neuroendocrine tumors are rare with an annual incidence of 2 in 100,000 people (Ram et al., 46:21-27, 2019). Up to 50% of patients with these tumors will develop carcinoid syndrome, which is characterized by symptoms caused by elevated levels of serotonin and most commonly include fatigue, flushing, wheezing, and non-specific gastrointestinal symptoms such as diarrhea and malabsorption (Pandit et al., StatPearls, 2022) (Fox et.al., 90:1224-1228, 2004). Over time, patients with carcinoid syndrome can develop carcinoid heart disease (CHD). CHD refers to the cardiac complications that occur when the vasoactive substances, such as serotonin, tachykinins, and prostaglandins, secreted from the carcinoid tumors. These complications most commonly include valvular abnormalities, but can also present as coronary artery damage, arrhythmias or direct myocardial injury (Ram et al., 46:21-27, 2019). While CHD is not typically an initial feature of carcinoid syndrome, it does eventually occur in up to 70% of patients with carcinoid tumors (Ram et al., 46:21-27, 2019) (Jin et.al., 146:65-73, 2021) (Macfie et.al., 224:665-669, 2022). CHD is associated with significant morbidity and mortality due to the risk of progressive heart failure (Bober et.al., 14:1179546820968101, 2020). In this case, we describe a 35-year-old Hispanic woman in South Texas with undiagnosed carcinoid syndrome for over 10 years that eventually progressed to severe CHD. In this patient’s case, we emphasize how lack of access to healthcare resulted in delay of diagnosis, appropriate treatment, and worsened prognosis in this young patient.

The Bone Cement Hypercoagulation Syndrome: Pathophysiology, Mortality, and Prevention.

Since Charnley introduced acrylic cement to seal metallic hip prostheses in the 1950s, reports of perioperative fatal cardiorespiratory and vascular dysfunctions have been published. Studies on humans and animals have shown neurogenic stimulation and substantial local and systemic activation of coagulation are caused by surgical bone marrow damage and chemical cell destruction by toxic monomeric methyl methacrylate from the implanted cement and other tissue-released substances. Venous blood-borne cell fragments and conjugates of activated cells from the surgical site are sequestered and trapped in the pulmonary microcirculation. A substantial hypercoagulation occurs in the lung circulation. Hypercoagulable blood is passed over to the arterial side and may cause vessel obliteration and organ damage. This process may affect the brain, heart, and kidneys and, through the release of vasoactive substances, introduce hemodynamic imbalances that can lead to fatal outcomes in susceptible populations such as elderly patients with hip fractures. The main underlying pathophysiologic processes leading to these occasionally devastating outcomes are a substantial activation of coagulation and cell destruction caused by the toxic substance released by curing bone cement and several vasoactive substances.

Potential mechanisms of acupuncture in enhancing cerebral perfusion of ischemic stroke.

Ischemic stroke is the predominant cause of long-term disability and death worldwide. It is attributable to the sudden interruption of regional cerebral blood flow, resulting in brain cell death and neurological impairment. Acupuncture is a widely used adjuvant treatment for ischemic stroke in China and shows promising efficacy in clinical practice. This review mainly focused on the evidence to illustrate several possible mechanisms of acupuncture therapy on cerebral perfusion in ischemic stroke. Studies have shown that acupuncture is probably effective in the enhancement of cerebral perfusion after ischemic stroke. It promotes the improvement of hemodynamics, the release of vasoactive substances, the formation of new blood vessels, as well as the restitution of microcirculation. Multiple factors may contribute to the variability in acupuncture's therapeutic effects, including the acupoint selection, stimulation frequency and intensity, and retaining needle time. Acupuncture has the potential to become a non-pharmacological adjuvant approach to enhance cerebral perfusion in ischemic stroke. Future studies are required to gain our insight into acupuncture as well as accelerate its clinical translation.

A novel mouse allergy tested model and its application for traditional Chinese medicine injections's allergy evaluation

When the drug induces the organism to produce a type Ⅰ allergic reaction, the combination of IgE and mast cells results in the degranulation of the mast cells. Release of vasoactive substances, increase in vascular permeability, and exudation of intravascular substances outside the blood vessels. Based on this pathophysiological mechanism, a mouse model that can objectively and quantitatively assess the allergic response to the injection has been established. ICR mice were sensitised by intraperitoneal injection of different doses of OVA once every two days for three times. 14 days after the last sensitization, a combination OVA solution of 4 times the sensitizing dose and Evans blue were injected intravenously into mice for the challenge. Compared with the normal group, OVA 0.625/2.5, 1.25/5, 2.5/10, 5/20 mg·kg~(-1) sensitized and challenged can induce allergic reactions mainly manifested by blue staining of the auricle in mice. Direct injection of OVA intravenously did not cause an auricular blue colouration reaction in mice. The passive cutaneous anaphylaxis reaction in mice was conducted with the aforementioned OVA-sensitized mouse serum, and there were obvious blue spots on the mouse's back. In addition, the content of anti-OVA-IgE in 5 mg·kg~(-1) OVA-sensitized mice was significantly increased. Ears and lungs of mice sensitized to OVA showed evident exudation inflammation. Significantly elevated inflammatory factors(VEGF and IL-10) were also detected in the serum of OVA-sensitized mice. The equivalent dose of OVA caused obvious allergic reactions in both guinea pigs and mice. Compared with nude mice, ICR and BALB/c mice are more sensitive to OVA sensitization. Injections of selected TCMI did not induce type Ⅰ allergic reactions in mice and guinea pigs, but there was a risk of inducing pseu-doallergic reactions in mice. The model is problematic and may well reflect the sensitization effect of allergens. It obtains the benefits of simple operation, accuracy, low cost, easy extension, and high repeatability. It is suitable for predicting and researching for IgE-dependent type Ⅰ allergic reactions.

Redox Homeostasis Alteration in Endothelial Mechanotransduction Monitored by Dual Stretchable Electrochemical Sensors.

In vivo, endothelial cells are permanently subjected to dynamic cyclic stretch and adapt to it through the release of vasoactive substances. Among them, reactive oxygen species (ROS) and nitric oxide (NO) are indispensable redox molecules, the contents of which and their ratio are closely implicated with endothelial redox homeostasis. However, simultaneous and quantitative monitoring of ROS and NO release in endothelial mechanotransduction remains a great challenge. Herein, a stretchable electrochemical device is developed with a dual electrode based on gold nanotubes decorated with uniform and tiny platinum nanoparticles. This hybrid nanostructure endows the sensor with high sensitivity toward both hydrogen peroxide (H2O2) (as the most stable ROS) and NO electrooxidation. Importantly, the two species can be well discriminated by applying different potentials, which allows simultaneous monitoring of H2O2 and NO release in stretch-induced endothelial mechanotransduction by the same device. The results of quantitative analysis suggest that endothelial redox homeostasis and its alteration are strongly related to vascular biomechanical and biochemical milieus. Further investigation reveals that the interplay of ROS and NO signaling has an important role in the regulation of endothelial redox state. This work will greatly facilitate the deep understanding of the molecular mechanism of endothelial dysfunction and vascular disorder.

Migraine Prevalence and Analysis of Dietary Habits in Relation to Headache in the Female Population: A Single-Center Study From Jeddah, Saudi Arabia

IntroductionLifestyle-related factors including dietary intake can significantly increase the chances of developing migraine. Some components of food items are thought to induce the release of vasoactive substances leading to the dilation of blood vessels, which in turn results in migraine episodes. This research aimed to assess the prevalence of migraine and examine the relation of the headache to the dietary patterns of female students and employees of King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) - Jeddah experiencing migraine attacks as well as to assess the relationship between the migraine attacks and the available dietary items served at the food outlets within the campus.MethodsTwo questionnaires were developed for this study. The first questionnaire was a short survey asking about the characteristics of headaches. This survey aimed to estimate the prevalence of migraine among female students and employees in KSAU-HS. Of the participants who filled the first questionnaire, those who met the International Classification of Headache Disorders (ICDH-III) criteria for migraine were given a second questionnaire to further understand the characteristics of their migraine headaches and to assess lifestyle and diet-related aggravating factors.ResultsThe final sample size for the calculated prevalence was 410; 352 were students and 58 were faculty members. It has been found that 165 (40.24%) participants of the KSAU-HS female population met the criteria for migraine. Two (2.2%) reported an association between chocolate consumption and headaches and seven (7.8%) reported a significant association between caffeine and headaches. No specific association was perceived by the respondents between migraine attacks and the following food items: citrus fruits, pickles, cheese, and dairy products.ConclusionOur study revealed that the widespread trends for excessive consumption of coffee and caffeinated beverages at food outlets within the educational institution are occult triggers for headache attacks in a significant portion of students with migraine. The recent shift in dietary habits in our community for excessive consumption of coffee and other tyramine-rich food items has negative consequences on productivity and the economy. Our results can be conceivably extrapolated to reflect the effect of dietary habits on other streams of society, including companies, firms, schools, and workplaces that are driven by the new dietary trends.

Carcinoid Crisis: A Misunderstood and Unrecognized Oncological Emergency.

Simple SummaryIn this review, the Authors are going to discuss the main highlights of the Carcinoid Crisis, an uncommon manifestation related to neuroendocrine tumors, focusing on the potential etiopathogenetic mechanisms, clinical implications, potential treatments and prophylaxis.Carcinoid Crisis represents a rare and extremely dangerous manifestation that can occur in patients with Neuroendocrine Tumors (NETs). It is characterized by a sudden onset of hemodynamic instability, sometimes associated with the classical symptoms of carcinoid syndrome, such as bronchospasm and flushing. Carcinoid Crisis seems to be caused by a massive release of vasoactive substances, typically produced by neuroendocrine cells, and can emerge after abdominal procedures, but also spontaneously in rare instances. To date, there are no empirically derived guidelines for the management of this cancer-related medical emergency, and the available evidence essentially comes from single-case reports or dated small retrospective series. A transfer to the Intensive Care Unit may be necessary during the acute setting, when the severe hypotension becomes unresponsive to standard practices, such as volemic filling and the infusion of vasopressor therapy. The only effective strategy is represented by prevention. The administration of octreotide, anxiolytic and antihistaminic agents represents the current treatment approach to avoid hormone release and prevent major complications. However, no standard protocols are available, resulting in great variability in terms of schedules, doses, ways of administration and timing of prophylactic treatments.

Tumor carcinoide primario de ovario. Reporte de caso

Los tumores neuroendocrinos primarios del ovario son raros y consisten en un grupo de neoplasias heterogéneas que expresan marcadores inmunohistoquímicos similares. Los tumores carcinoides son las neoplasias neuroendocrinas más comunes, la mayoría surgen en el tracto gastrointestinal y broncopulmonar. Los tumores carcinoides primarios del ovario son entidades raras que representan aproximadamente 0,3% de todos los tumores carcinoides y menos del 0,1% de todas las neoplasias ováricas, con buen pronóstico y generalmente limitados al parénquima ovárico. Estos tumores surgen del sistema de células neuroendocrinas del estroma, epitelio superficial y teratomas ováricos. Las manifestaciones clínicas, en la mayoría de los casos, están asociadas con liberación de sustancias vasoactivas que causan síntomas, como enrojecimiento cutáneo, diarrea y broncoespasmo. Para realizar el diagnóstico es necesario el uso de imágenes radiológicas multimodales y análisis bioquímicos de marcadores tumorales neuroendocrinos. El tratamiento de primera línea es la resección del tumor siempre que sea posible. El pronóstico es generalmente favorable, excepto en algunos casos con metástasis. Se presenta un caso de tumor carcinoide primario de ovario.

Reduced blood flow in fibromyotic muscles during ultrasound therapy

The muscle blood flow (MBF) in m. trapezius was studied in 7 subjects with fibromyotic pain syndrome before and during treatment with ultrasound (1 Watt/cm2) and during placebo treatment, using the local 133Xe-washout technique. MBF in the fibromyotic muscles was significantly reduced during ultrasound treatment (p less than 0.05) compared to the blood flow before the treatment and during placebo treatment 1.57 +/- SEM 0.52 and 2.51 +/- SEM 0.43 ml/100 g/min, respectively. In 6 normal trapezius muscles the mean MBF was 2.30 +/- SEM 0.44 ml/100 g/min before ultrasound treatment and 2.31 +/- SEM 0.41 ml/100 g/min during ultrasound therapy. MBF decreased in a lidocaine blocked fibromyotic muscle during ultrasound treatment while no effect on MBF was detectable during ultrasonic treatment a normal lidocaine pretreated muscle. It is concluded that ultrasound treatment decreases MBF in fibromyotic muscles and that this is paradoxical effect of ultrasound might be due to a direct effect on the vessels or a local release of vasoactive substances in the fibromyotic muscles.

May sevoflurane prevent the development of neurogenic pulmonary edema and improve the outcome? Or as a new sedation method for severe brain injury patients

Neurogenic pulmonary edema (NPE) is a life-threatening complication that develops rapidly and dramatically after injury to the central nervous system (CNS). Severe primary brain injury and subsequent secondary brain injury cascade events are thought to be involved in the development of NPE. Activation of the sympathetic nervous system and release of vasoactive substances are also essential prerequisites for NPE. We hypothesize that sevoflurane may be an effective treatment for preventing the development of NPE. Sevoflurane may play a role in protecting brain and lung tissue after acute brain injury through its sympatholytic, antioxidative, ion channel stabilizing, anti-inflammatory, anti-apoptotic, and pulmonary protection effects. It has the potential to be used as a sedative in the neurosurgical intensive care unit (NICU), which can help maintain nervous system and cardiopulmonary function in patients with acute brain injury to improve prognosis. Sevoflurane also has the advantages of fast induction of anesthesia, rapid drug metabolism, little interference to the cardiovascular system, and controllable depth of anesthesia. If our hypothesis is supported by further experiments, use of sevoflurane may open a new door for the treatment of acute brain injury and NPE.

Brain Edema: Newer Concept of Treatment

AbstractBrain edema is excess accumulation of water in intracellular or extracellular spaces of the brain. It may be due to traumatic brain injury, neoplasm, infection, or following surgery. Advent of electron microscope and molecular pathophysiology of fluid transport through blood–brain barrier has elucidated the mechanism of edema formation, that is, ion channels and transport of fluid into extracellular space. Currently approved treatments, such as decompressive craniectomy and osmotherapy, controlled hyperventilation, and administration of diuretics, were developed prior to any knowledge of modern cerebral edema pathophysiology. These therapies attempt to manage downstream end-stage events without directly attenuating the underlying molecular mechanisms of cerebral edema. Next few years will yield new knowledge of how particular proteins drive edema influx, paving the way for rationally designed therapeutics that directly target key steps in cerebral edema formation, thereby achieving what currently approved therapies do not. Pharmacological agents which can block edema formation are being tried experimentally and clinically. Development in imaging, that is, computed tomography and diffusion tensor magnetic resonance imaging, has helped in antemortem assessment of evolution and resolution of brain edema as a dynamic pathophysiology. Animal studies shows release of vasoactive substances, that is, histamine, serotonin, adrenaline, nitric oxide, substance P, prostaglandins, tumor necrosis factor-α, and cytokines, in the injured brain results in activation of inflammatory cascade, which is the important cause of brain edema.

Measuring the Nitroglycerine-Induced Vasodilation in Carotid Arteries

Introduction: Nitroglycerin is a fast-acting drug that rapidly dilates coronary arteries and thus increases blood flow to these vessels, and increases the blood flow through the lateral vessels to low blood areas. It also reduces both end diastolic pressure and volume of the left ventricular. However, the effect of nitroglycerin on the circulation hemodynamic is not known. Carotid artery is an artery on each side of the head and neck that supplying blood to the brain, face, scalp, skull, neck and meninges. The purpose of this study was to evaluate the influence of the Nitroglycerin on the blood velocity of the carotid artery. Materials and Methods: Right carotid artery (common carotid artery 2 cm before the bifurcation, beginning of the internal and external carotid arteries) of 10 healthy subjects (age, 24±4 years) was scanned longitudinally with an ultrasound system (esaote Mylab 60) equipped with linear probe (4-13 MHz). Pulse wave Doppler images of blood velocity of the carotid arteries were recorded before and after taking a sublingual nitroglycerin pill. The blood velocity waveforms were extracted from sonograms over three cardiac cycles by using a custom analysis programs written in MATLAB. The effect of nitroglycerin on the carotid blood velocity was evaluated. Results: According to the results, the carotid blood velocities changed significantly after administration the nitroglycerin. The peak systolic blood flow velocity of the CCA and ICA decreased 15% ± 9 and 20%± 16 after taking the pill, respectively. The end diastolic velocity of the blood flow in the CCA and ICA decreased 19% ± 12 and 16%± 11, respectively. The dicrotic notch of the CCA and ECA descended 24% ± 12 and 24% ± 22, respectively. There was not shown significant difference in the heart rate of the subjects before and after nitroglycerin administration. Conclusion: According to presented results, nitroglycerin reduces both peak systolic and end diastolic blood velocity of the CCA and ICA. It seems that this hemodynamic change in the blood velocity caused by nitroglycerin might be a fast response of the carotid artery to the release of vasoactive substances such as nitric oxide (NO) from the endothelium.

The effects of proton pump inhibitor on hepatic vascular responsiveness and hemodynamics in cirrhotic rats

BackgroundLiver cirrhosis is associated with increased intrahepatic resistance due to hepatic fibrosis and exaggerated vasoconstriction. Recent studies have indicated that proton pump inhibitors (PPIs), in addition to acid suppression, modulate vasoactive substances and vasoresponsiveness. PPIs are frequently prescribed in patients with cirrhosis due to a higher prevalence of peptic ulcers, however other impacts are unknown. MethodsLiver cirrhosis was induced in Sprague–Dawley rats with common bile duct ligation (BDL). On the 29th day after BDL and after hemodynamic measurements, the intrahepatic vascular responsiveness to high concentrations of endothelin-1 (ET-1) was evaluated after preincubation with (1) Krebs solution (vehicle), (2) esomeprazole (30 μM), or (3) esomeprazole plus Nω-nitro l-arginine (NNA, a non-selective NO synthase (NOS) inhibitor, 10−4 M). After perfusion, the hepatic protein expressions of endothelial NOS (eNOS), inducible NOS (iNOS), cyclooxygenase (COX)-1, COX-2, endothelin-1, DDAH-1 (dimethylarginine dimethylaminohydrolase-1, ADMA inhibitor), DDAH-2, ADMA (asymmetrical dimethyl arginine, NOS inhibitor) were evaluated. In the chronic model, the BDL rats received (1) vehicle; or (2) esomeprazole (3.6 mg/kg/day, oral gavage) from the 1st to 28th day after BDL. On the 29th day and after hemodynamic measurements, plasma liver biochemistry and liver fibrosis were evaluated. ResultsEsomeprazole did not affect hepatic ET-1 vasoresponsiveness. The hepatic protein expressions of the aforementioned factors were not significantly different among the groups. There were no significant differences in hemodynamics, liver biochemistry and hepatic fibrosis after chronic esomeprazole administration. ConclusionPPIs did not affect hepatic vasoresponsiveness or the release of vasoactive substances. Furthermore, they did not influence hemodynamics, liver biochemistry or severity of hepatic fibrosis in the cirrhotic rats.

H2O2 Regulates Arachidonic Acid‐induced TRPV4‐mediated Vasodilation in Human Coronary Arterioles

Previous studies have demonstrated that arachidonic acid (AA) induces potent dilation of human coronary arterioles (HCAs) through the activation of endothelial TRPV4 channels followed by endothelial hyperpolarization or release of vasoactive substances. In addition, TRPV4‐mediated vasodilatory response to flow is augmented in HCAs from subjects with coronary artery disease (CAD), a condition associated with increased H2O2 production. However, the role of H2O2 in regulation of TRPV4 function remains to be elucidated. Therefore, we designed this study to examine the effect of endogenous H2O2 on TRPV4 function. Coronary arterioles (~150 μm ID), isolated from atrial tissues from patients with CAD, were cannulated and pressurized at 60 mmHg for videomicroscopic measurement of vessel diameters. In arterioles preconstricted with endothelin‐1, AA (10−11 to 10−6 M) elicited a concentration‐dependent dilation (maximal dilation: 84±5%, n=5), and this dilation was largely blocked by HC‐067047 (10−6 M), a TRPV4 antagonist (17±4%, n=5). Intraluminal incubation of HCAs with catalase, a H2O2 –scavenging enzyme (500 units/mL), also markedly reduced the dilation to AA (57±5% vs. 85±5% of control, n=8). The EET antagonist 14,15‐EEZE (10−5 M) failed to attenuate AA‐induced dilation (64±6% vs. 70±7% of control, n=5), suggesting that P450 metabolites of AA such as EETs do not significantly contribute to endothelial TRPV4‐mediated response. Together, these data provide evidence that H2O2 regulates AA‐induced TRPV4‐mediated dilation in HCAs.Support or Funding InformationThis work was supported by NIH R01‐HL096647 (to David X Zhang)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Possible mechanisms of diverse spaceflight effects on endothelial function in different vascular beds

Possible mechanisms of diverse spaceflight effects on endothelial function in different vascular beds