Comparison of the apoptotic effects of topically applied papaverine, diltiazem, and nitroprusside to internal thoracic artery

Abstract Objective: To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside. Methods: Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis. Results: Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups. Conclusion: The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.

Eventos adversos durante transporte intra-hospitalar de pacientes críticos em hospital de grande porte / Adverse events during intrahospital transport of critically ill patients in a large hospital

RESUMO Objetivo: Descrever a incidência de eventos clínicos e não clínicos durante o transporte intra-hospitalar de pacientes críticos e analisar os fatores de risco associados. Métodos: Estudo de coorte, com coleta retrospectiva, no período de outubro de 2016 a outubro de 2017, tendo sido analisados todos os transportes intra-hospitalares para fins diagnósticos e terapêuticos em hospital de grande porte, que contava com seis unidades de terapia intensiva adulto, sendo avaliados os eventos adversos e os fatores de risco relacionados. Resultados: No período, foram realizados 1.559 transportes intra-hospitalares, em 1.348 pacientes, com média de idade de 66 ± 17 anos, tempo médio de transporte de 43 ± 34 minutos. Durante o transporte, 19,8% dos pacientes estavam em uso de drogas vasoativas; 13,7% em uso de sedativos e 10,6% estavam sob ventilação mecânica. Eventos clínicos ocorreram em 117 transportes (7,5%) e não clínicos em 125 transportes (8,0%). Falhas de comunicação foram prevalentes, no entanto, aplicando-se análise multivariada, uso de sedativos, noradrenalina e nitroprussiato, e o tempo de transporte maior que 36,5 minutos estiveram associados a eventos adversos clínicos. Uso de dobutamina e tempo de transporte superior a 36,5 minutos estiveram associados a eventos não clínicos. Ao final do transporte, 98,1% dos pacientes apresentaram condições clínicas inalteradas em relação ao seu estado basal. Conclusão: Transportes intra-hospitalares estão relacionados à alta incidência de eventos adversos; o tempo de transporte e a utilização de sedativos e drogas vasoativas estiveram relacionados a esses eventos.

ABSTRACT Objective: To describe the incidence of clinical and non-clinical events during intrahospital transport of critically ill patients and to analyze the associated risk factors. Methods: Cohort study with retrospective data collected from October 2016 to October 2017. All cases of intrahospital transport for diagnostic and therapeutic purposes in a large hospital with six adult intensive care units were analyzed, and the adverse events and related risk factors were evaluated. Results: During the study period, 1,559 intrahospital transports were performed with 1,348 patients, with a mean age of 66 ± 17 years and a mean transport time of 43 ± 34 minutes. During transport, 19.8% of the patients were using vasoactive drugs; 13.7% were under sedation; and 10.6% were under mechanical ventilation. Clinical events occurred in 117 transports (7.5%), and non-clinical events occurred in 125 (8.0%) transports. Communication failures were prevalent; however, the multivariate analysis showed that the use of sedatives, noradrenaline and nitroprusside and a transport time greater than 36.5 minutes were associated with adverse clinical events. The use of dobutamine and a transport time greater than 36.5 minutes were associated with non-clinical events. At the end of transport, 98.1% of the patients presented unchanged clinical conditions compared with baseline. Conclusion: Intrahospital transport is related to a high incidence of adverse events, and transport time and the use of sedatives and vasoactive drugs were related to these events.

Crises hipertensivas: definindo a gravidade e o tratamento / Hipertensive crises: defining he severity and treatment

As situações clínicas de aumento súbito da pressão arterial (PA) que caracterizam as crises hipertensivas são comuns na prática clínica, principalmente nas consultas realiza-das no pronto atendimento, portanto, o diagnóstico adequado é essencial para o melhor tratamento e desfecho clínico. A crise hipertensiva é definida pelo aumento súbito na PA (≥180 /120 mmHg) e a necessidade da redução agressiva da PA depende da gravidade da situação clinica associada. A presença de lesões novas ou progressivas em órgãos-alvo e risco iminente de morte definem as emergências hipertensivas que requerem tratamento imediato visando a rápida redução da pressão arterial, porém, não, necessariamente, a níveis normais. Na maioria dos casos, a velocidade do aumento da PA é mais importante que o nível real da PA, portanto, é fundamental que haja avaliação clínica para o diagnóstico preciso dessas condições clínicas, as quais incluem encefalopatia hipertensiva, síndromes coronarianas agudas, edema agudo dos pulmões, acidente vascular cerebral, dissecção de aorta e eclampsia. As metas para diminuição da PA para as emergências hipertensivas, de acordo com o órgão-alvo envolvido, são revisadas pelas atuais diretrizes brasileiras e ame-ricanas de hipertensão. O tratamento das emergências hipertensivas inclui vasodilatadores de ação direta e bloqueadores adrenérgicos já consagrados, entretanto, evidências recentes mostram o benefício do uso de novos fármacos ainda não disponíveis em nosso meio

The clinical conditions of an acute rise in blood pressure (BP) that characterize hyperten-sive crises are common in clinical practice, particularly in consultations that take place in the emergency room. Therefore the correct diagnosis is important for the best treatment and clinical outcome. Hypertensive crisis is defined as a sudden rise in BP (≥ 180/120 mmHg), and the need for aggressive reduction of BP depends on the severity of the associated clinical situation. The presence of new or progressive target organ injury and imminent risk of death define hypertensive emergencies requiring immediate treatment aimed at rapid reduction of blood pressure, not ne-cessarily to normal levels. In most cases, the speed of the rise in BP is more important than the actual level of BP, and clinical evaluation is essential for the accurate diagnosis of these clinical conditions, which include hypertensive encephalopathy, acute coronary syndromes, pulmonary edema, stroke, aortic dissection, and eclampsia. The goals of BP reduction for hypertensive emergencies, according to the target organ involved, have been reviewed by the current Brazi-lian and American guidelines on hypertension. Treatment of hypertensive emergencies includes direct action vasodilators and adrenergic blockers, which are already well established, but recent evidence shows the benefit of the use of new drugs, not yet available in Brazil

The role of potassium channels in the endothelial dysfunction induced by periodontitis

Abstract Objective: Periodontitis is associated with endothelial dysfunction, which is clinically characterized by a reduction in endothelium-dependent relaxation. However, we have previously shown that impairment in endothelium-dependent relaxation is transient. Therefore, we evaluated which mediators are involved in endothelium-dependent relaxation recovery. Material and methods: Rats were subjected to ligature-induced experimental periodontitis. Twenty-one days after the procedure, the animals were prepared for blood pressure recording, and the responses to acetylcholine or sodium nitroprusside were obtained before and 30 minutes after injection of a nitric oxide synthase inhibitor (L-NAME), cyclooxygenase inhibitor (Indomethacin, SC-550 and NS- 398), or calcium-dependent potassium channel blockers (apamin plus TRAM- 34). The maxilla and mandible were removed for bone loss analysis. Blood and gingivae were obtained for C-reactive protein (CRP) and myeloperoxidase (MPO) measurement, respectively. Results: Experimental periodontitis induces bone loss and an increase in the gingival MPO and plasmatic CRP. Periodontitis also reduced endothelium-dependent vasodilation, a hallmark of endothelial dysfunction, 14 days after the procedure. However, the response was restored at day 21. We found that endothelium-dependent vasodilation at day 21 in ligature animals was mediated, at least in part, by the activation of endothelial calcium-activated potassium channels. Conclusions: Periodontitis induces impairment in endothelial-dependent relaxation; this impairment recovers, even in the presence of periodontitis. The recovery is mediated by the activation of endothelial calcium-activated potassium channels in ligature animals. Although important for maintenance of vascular homeostasis, this effect could mask the lack of NO, which has other beneficial properties.

Application of Tetrode Technology for Analysis of Changes in Neural Excitability of Medial Vestibular Nucleus by Acute Arterial Hypotension / 대한평형의학회지

OBJECTIVES: Excitability o medial vestibular nucleus (MVN) in the brainstem can be affected by changes in the arterial blood pressure. Several animal studies have demonstrated that acute hypotension results in the alteration of multiunit activities and expression of cFos protein in the MVN. In the field of extracellular electrophysiological recording, tetrode technology and spike sorting algorithms can easily identify single unit activity from multiunit activities in the brain. However, detailed properties of electrophysiological changes in single unit of the MVN during acute hypotension have been unknown. METHODS: Therefore, we applied tetrode techniques and electrophysiological characterization methods to know the effect of acute hypotension on single unit activities of the MVN of rats. RESULTS: Two or 3 types of unit could be classified according to the morphology of spikes and firing properties of neurons. Acute hypotension elicited 4 types of changes in spontaneous firing of single unit in the MVN. Most of these neurons showed excitatory responses for about within 1 minute after the induction of acute hypotension and then returned to the baseline activity 10 minutes after the injection of sodium nitroprusside. There was also gradual increase in spontaneous firing in some units. In contrast small proportion of units showed rapid reduction of firing rate just after acute hypotension. CONCLUSIONS: Therefore, application of tetrode technology and spike sorting algorithms is another method for the monitoring of electrical activity of vestibular nuclear during acute hypotension.

Potentiation of endothelium-dependent vasorelaxation of mesenteric arteries from spontaneously hypertensive rats by gemigliptin, a dipeptidyl peptidase-4 inhibitor class of anti-diabetic drug

Dipeptidyl peptidase4 (DPP4) inhibitors such as gemigliptin are anti-diabetic drugs elevating plasma concentration of incretins such as GLP-1. In addition to the DPP4 inhibition, gemigliptin might directly improve the functions of vessels under pathological conditions. To test this hypothesis, we investigated whether the acetylcholine-induced endothelium dependent relaxation (ACh-EDR) of mesenteric arteries (MA) are altered by gemigliptin pretreatment in Spontaneous Hypertensive Rats (SHR) and in Wistar-Kyoto rats (WKY) under hyperglycemia-like conditions (HG; 2 hr incubation with 50 mM glucose). ACh-EDR of WKY was reduced by the HG condition, which was significantly recovered by 1 µM gemigliptin while not by saxagliptin and sitagliptin up to 10 µM. The ACh-EDR of SHR MA was also improved by 1 µM gemigliptin while similar recovery was observed with higher concentration (10 µM) of saxagliptin and sitagliptin. The facilitation of ACh-EDR by gemigliptin in SHR was not observed under pretreatment with NOS inhibitor, L-NAME. In the endotheliumdenuded MA of SHR, sodium nitroprusside induced dose-dependent relaxation was not affected by gemigliptin. The ACh-EDR in WKY was decreased by treatment with 30 µM pyrogallol, a superoxide generator, which was not prevented by gemigliptin. Exendin-4, a GLP-1 analogue, could not enhance the ACh-EDR in SHR MA. The present results of ex vivo study suggest that gemigliptin enhances the NOS-mediated EDR of the HG-treated MA as well as the MA from SHR via GLP-1 receptor independent mechanism.

Antihypertensive effect of ethanol extracts of Aralia elata in spontaneously hypertensive rats

Antihypertensive effects of ethanol extracts of Aralia elata (Miq.) Seem. (AE) were investigated in spontaneously hypertensive rats (SHR). SHR aged 14 weeks were treated for 8 weeks with AE (10 or 50 mg/kg/day) or amlodipine besylate (Am; 10 mg/kg/day) orally. Hypertension results in injury to several organs and can produce a significant increase in malondialdehyde (MDA) content as a result of lipid peroxidation and endothelial dysfunction. In this study, oral administration of AE and Am significantly reduced systolic blood pressure, organ weight index, and MDA content in tissues but increased significantly the plasma nitrite and nitrate concentrations. The endothelium-dependent relaxant activities of acetylcholine (10⁻¹⁰–10⁻³ M) in norepinephrine (NE)-precontracted aorta were increased in AE- and Am-treated rats. Particularly strong endothelium-dependent relaxant activities were observed in AE-treated (50 mg/kg) rats. The endothelium-independent relaxant activities of sodium nitroprusside (10⁻¹⁰–10⁻³ M) in NE-precontracted aorta were not changed. The results of this study suggest that AE has both antihypertensive and end-organ protective effects in SHR.

Influence of sodium nitroprusside on expressions of FBXL5 and IRP2 in SH-SY5Y cells / 生理学报

Iron accumulation in the brain is associated with the pathogenesis of Parkinson's disease (PD). Misexpression of some iron transport and storage proteins is related to iron dyshomeostasis. Iron regulatory proteins (IRPs) including IRP1 and IRP2 are cytosolic proteins that play important roles in maintaining cellular iron homeostasis. F-box and leucine-rich repeat protein 5 (FBXL5) is involved in the regulation of iron metabolism by degrading IRP2 through the ubiquitin-proteasome system. Nitric oxide (NO) enhances the binding activity of IRP1, but its effect on IRP2 is ambiguous. Therefore, in the present study, we aim to determine whether sodium nitroprusside (SNP), a NO donor, regulates FBXL5 and IRP2 expression in cultured SH-SY5Y cells. MTT assay revealed that treatment of SNP attenuated the cell viability in a dose-dependent manner. Flow cytometry test showed that 100 and 300 μmol/L SNP administration significantly reduced the mitochondrial membrane potential by 45% and 60%, respectively. Moreover, Western blotting analysis demonstrated that 300 μmol/L SNP significantly increased FBXL5 expression by about 39%, whereas the expression of IRP2 was decreased by 46%, correspondingly. These findings provide evidence that SNP could induce mitochondrial dysfunction, enhance FBXL5 expression and decrease IRP2 expression in SH-SY5Y cells.

Dual control of the vestibulosympathetic reflex following hypotension in rats

Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP. SNP-induced hypotension led to increased pERK expression in the medial vestibular nucleus (MVN), rostral ventrolateral medullary nucleus (RVLM) and the IMC, as well as increased blood epinephrine levels. We co-administered either a glutamate receptor agonist or a glutamate receptor antagonist to the MVN or the RVLM. The administration of the glutamate receptor agonists, AMPA or NMDA, to the MVN or RVLM led to elevated blood pressure, increased pERK expression in the IMC, and increased blood epinephrine levels. Administration of the glutamate receptor antagonists, CNQX or MK801, to the MVN or RVLM attenuated the increased pERK expression and blood epinephrine levels caused by SNP-induced hypotension. These results suggest that two components of the pathway which maintains blood pressure are involved in the VSR induced by SNP. These are the neurogenic control of blood pressure via the RVLM and the humoral control of blood pressure via epinephrine release from the adrenal medulla.

Role of NO in arterial vascular function of intertidal fish (Girella laevifrons) and marine fish (Isacia conceptionis) / Papel do NO na função vascular arterial de peixes entremarés (Girella laevifrons) e peixes marinhos (Isacia conceptionis)

Abstract Previous studies performed in intertidal fish (Girella laevifrons),as well as marine fish (Isacia conceptionis), showed that acetylcholine (ACh) produced contractions mediated by cyclooxygenases that were dependent on the area and potency of contraction in several arterial vessels. Given that the role of nitric oxide is poorly understood in fish, the objective of our study was to evaluate the role of nitric oxide in branchial afferent (ABA), branchial efferent (ABE), dorsal (DA) and mesenteric (MA) arterial vessels from both Girella laevifrons and Isacia conceptionis. We studied afferent and efferent branchial, dorsal and mesenteric arteries that were dissected from 6 juvenile specimens. Isometric tension studies were done using dose response curves (DRC) for Ach (10–13 to 10–3 M) and blockade with L-NAME (10–5 M), and DRC for sodium nitroprusside (SNP, a donor of NO). L-NAME produced an attenuation of the contractile response in the dorsal, afferent and efferent branchial arteries and a potentiation of the contraction in the MA. SNP caused 70% dilation in the mesenteric artery and 40% in the dorsal artery. Our results suggest that Ach promotes precarious dilatation in MA mediated by NO; data that is supported by the use of sodium nitroprusside. In contrast, in the vessels DA, ABA and EBA our results support that the pathway Ach-NO-relaxation is absent in both species.

Resumo Estudos anteriores, realizados no peixe intertidal (Girellalaevifrons) no peixe marinho (Isacia conceptionis), mostram que a acetilcolina (Ach) provoca contrações mediadas por ciclooxigenases que eram dependentes da área e potencia da contração em vários vasos arteriais. Tendo em conta que o papel do óxido nítrico é mal compreendido em peixes, o objetivo do nosso estudo foi avaliar o papel do óxido nítrico em vasos arteriais de ambos os peixes Girella laevifrons e Isacia conceptionis. Nós estudamos os vasos aferente, branquial (ABA), eferente branquial (ABE), dorsal (DA) e mesentérica (MA), que foram dissecadas de seis espécimes juvenis. Estudos de tensão isométrica foram realizados utilizando as curvas de dose-resposta (DRC) para Ach (10–13 a 10–3M) e bloqueio com L-NAME (10–5 M), e na DRC para o nitroprussiato de sódio (SNP, doador do NO). L- NAME produziu uma atenuação da resposta contrátil nas artérias dorsais, aferentes e eferentes branquial e uma potenciação da contração no MA. SNP causaram 70% da dilatação da artéria mesentérica e 40% na artéria dorsal. Nossos resultados sugerem que Ach promove dilatação precária em MA mediada por NO; dados que é suportada pela utlilização de nitroprussiato de sódio. Em contraste, nos vasos de DA, ABA e EBA nossos resultados suportam que a via de Ach-NO-relaxamento está ausente em ambas as espécies.

Sodium nitroprusside has leishmanicidal activity independent of iNOS

Abstract: INTRODUCTION: Leishmaniasis is a zoonotic disease caused by protozoa of the genus Leishmania . Cutaneous leishmaniasis is the most common form, with millions of new cases worldwide each year. Treatments are ineffective due to the toxicity of existing drugs and the resistance acquired by certain strains of the parasite. METHODS: We evaluated the activity of sodium nitroprusside in macrophages infected with Leishmania (Leishmania) amazonensis . Phagocytic and microbicidal activity were evaluated by phagocytosis assay and promastigote recovery, respectively, while cytokine production and nitrite levels were determined by ELISA and by the Griess method. Levels of iNOS and 3-nitrotyrosine were measured by immunocytochemistry. RESULTS: Sodium nitroprusside exhibited in vitro antileishmanial activity at both concentrations tested, reducing the number of amastigotes and recovered promastigotes in macrophages infected with L. amazonensis . At 1.5µg/mL, sodium nitroprusside stimulated levels of TNF-α and nitric oxide, but not IFN-γ. The compound also increased levels of 3-nitrotyrosine, but not expression of iNOS, suggesting that the drug acts as an exogenous source of nitric oxide. CONCLUSIONS: Sodium nitroprusside enhances microbicidal activity in Leishmania -infected macrophages by boosting nitric oxide and 3-nitrotyrosine.

Cyanide toxicity during cardiopulmonary bypass with small dose of nitroprusside: a case report / 대한마취과학회지

Sodium nitroprusside (SNP) is an anti-hypertensive drug, commonly used to decrease the systemic vascular resistance and lower the blood pressure. When the amount of cyanide generated by the SNP exceeds the metabolic capacity for detoxification, cyanide toxicity occurs. Under general anesthesia and cardiopulmonary bypass (CPB), it may be difficult to detect the development of cyanide toxicity. In cardiac surgical patients, hemolysis, hypothermia and decreased organ perfusion, which emphasize the risk of cyanide toxicity, may develop as a consequence of CPB. In particular, hemolysis during CPB may cause an unexpected overproduction of cyanide due to free hemoglobin release. We experienced a patient who demonstrated SNP tachyphylaxis and cyanide toxicity during CPB, even though the total amount of SNP administered was much lower than the recommended dose. We therefore report this case with a review of the relevant literature.

Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-κB/PGC-1α pathways / 华中科技大学学报（医学）（英德文版）

SRT1720, a new discovered drug, was reported to activate silent information regulator 1 (SIRT1) and inhibit the chondrocyte apoptosis. However, the underlying mechanism remains elusive. In the present study, the chondrocytes were extracted from the cartilage tissues of New Zealand white rabbits, cultured in the presence of sodium nitroprusside (SNP) (2.5 mmol/L) and divided into five groups: 1, 5, 10, and 20 μmol/L SRT1720 groups and blank control group (0 μmol/L SRT1720). MTT assay was used to detect the chondrocyte viability and proliferation, and DAPI staining and flow cytometry to measure the chondrocyte apoptosis. The expression levels of SIRT1, p53, NF-κB/p65, Bax, and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) were detected by Western blotting and the expression levels of SIRT1, type II collagen, and aggrecan mRNA by RT-PCR. The results showed that in the SRT1720-treated groups, the nuclei of chondrocytes were morphologically intact and had uniform chromatin. In the blank control group, nuclear rupture into debris was observed in chondrocytes. With the SRT1720 concentration increasing, the chondrocyte viability increased, the apoptosis rate decreased, the protein expression levels of SIRT1 and PGC-1α and the mRNA expression levels of type II collagen and aggrecan increased ({ptP}<0.05), and the expression levels of p53, NF-κB and bax decreased (P<0.05). It was suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF-κB/PGC-1α pathways.

Gintonin facilitates catecholamine secretion from the perfused adrenal medulla

The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to 30 µg/ml), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine (1 µM, an autonomic ganglionic bloker), pirenzepine (2 µM, a muscarinic M₁ receptor antagonist), Ki14625 (10 µM, an LPA₁/₃ receptor antagonist), amiloride (1 mM, an inhibitor of Na⁺/Ca²⁺ exchanger), a nicardipine (1 µM, a voltage-dependent Ca²⁺ channel blocker), TMB-8 (1 µM, an intracellular Ca²⁺ antagonist), and perfusion of Ca²⁺-free Krebs solution with 5mM EGTA (a Ca²⁺chelater), while was not affected by sodium nitroprusside (100 µM, a nitrosovasodialtor). Interestingly, LPA (0.3~3 µM, an LPA receptor agonist) also dose-dependently enhanced the CA secretion from the adrenal medulla, but this facilitatory effect of LPA was greatly inhibited in the presence of Ki 14625 (10 µM). Moreover, acetylcholine (AC)-evoked CA secretion was greatly potentiated during the perfusion of gintonin (3 µg/ml). Taken together, these results demonstrate the first evidence that gintonin increases the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. This facilitatory effect of gintonin seems to be associated with activation of LPA- and cholinergic-receptors, which are relevant to the cytoplasmic Ca²⁺ increase by stimulation of the Ca²⁺ influx as well as by the inhibition of Ca²⁺ uptake into the cytoplasmic Ca²⁺ stores, without the increased nitric oxide (NO). Based on these results, it is thought that gintonin, one of ginseng components, can elevate the CA secretion from adrenal medulla by regulating the Ca²⁺ mobilization for exocytosis, suggesting facilitation of cardiovascular system. Also, these findings show that gintonin might be at least one of ginseng-induced hypertensive components.

AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis

PURPOSE: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. MATERIALS AND METHODS: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. RESULTS: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. CONCLUSION: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.

Direct vascular actions of quercetin in aorta from renal hypertensive rats

BACKGROUND: Chronic treatment with the dietary flavonoid quercetin is known to lower blood pressure and restore endothelial dysfunction in animal models of hypertension. This study investigated the direct effects of quercetin on vascular response in chronic 2-kidney, 1-clip (2K1C) renal hypertensive rats. The effects of antioxidant vitamin ascorbic acid on the vasoreactivity were also examined. METHODS: 2K1C renal hypertension was induced by clipping the left renal artery; age-matched rats that received sham treatment served as controls. Thoracic aortae were mounted in tissue baths for the measurement of isometric tension. RESULTS: Relaxant responses to acetylcholine were significantly attenuated in 2K1C rats in comparison with sham rats. Quercetin or ascorbic acid augmented acetylcholine-induced relaxation in 2K1C rats, whereas no significant differences were noted in sham rats. The relaxation response to sodium nitroprusside was comparable between 2K1C and sham rats, and sodium nitroprusside-induced relaxation was not altered by quercetin or ascorbic acid in either group. The contractile response to phenylephrine was significantly enhanced in 2K1C rats compared with sham rats. Phenylephrine-induced contraction was inhibited by pretreatment with quercetin or ascorbic acid in 2K1C rats, whereas neither chemical affected responses in sham rats. N(w)-nitro-L-arginine methyl ester markedly augmented the contractile response to phenylephrine in sham rats, whereas no significant differences were observed in 2K1C rats. Quercetin or ascorbic acid did not affect phenylephrine-induced contraction in the presence of N(w)-nitro-L-arginine methyl ester in either 2K1C or sham rats. CONCLUSION: Acute exposure to quercetin appears to improve endothelium-dependent relaxation and inhibit the contractile response, similar to the effect of ascorbic acid in 2K1C hypertension. These results partially explain the vascular beneficial effects of quercetin in renal hypertension.

Sodium nitroprusside: low price and safe drug to control BP during thrombolysis in AIS / Nitroprussiato de sódio: uma droga segura e de baixo custo para o controle de PA durante a trombólise em AVC isquêmico

This study analyzes the use of sodium nitroprusside (SN) as an option to reduce blood pressure (BP) below 180/105 mmHg during the management of acute ischemic stroke (AIS) in patients submitted to intravenous thrombolysis.Method The sample was composed by 60 patients who had AIS and were submitted to intravenous rtPA, split in two groups: half in the control group (CG) with BP < 180/105 mmHg and half in SN group with BP > 180/105 mmHg. Outcome variables were any hemorrhagic transformation (HT); the presence of symptomatic HT, National Institute of Health Stroke Scale (NIHSS) after 24 hours of treatment; the independence on discharge and death until three months after stroke onset.Results There were no statistical differences between both groups to any of the outcome variables analyzed.Conclusion The SN might be safe for BP control during thrombolysis to AIS.

Este estudo analisa o uso de nitroprussiato de sódio (NS) como uma opção para reduzir a pressão arterial (PA) durante o tratamento do AVC isquêmico agudo (AVCi) em pacientes submetidos à trombólise intravenosa (rtPA).Método A amostra foi composta por 60 pacientes que tiveram AVCi e foram submetidos a rtPA, dividida em dois grupos: 30 pacientes no grupo controle (GC), com PA < 180/105 mmHg e 30 pacientes no grupo NS com PA > 180/105 mmHg. As variáveis analisadas foram qualquer transformação hemorrágica (TH); a presença de TH sintomática, NIHSS após 24 horas de tratamento; a independência na alta e morte até três meses após o AVCi.Resultados Não houve diferença estatística entre os dois grupos para qualquer das variáveis de desfecho analisadas.Conclusão O NS pode ser seguro para o controle da pressão arterial durante a trombólise no AVCi.

Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats / Efeitos de uma Sessão de Exercício Resistido sobre o Músculo Liso Vascular de Ratos Hipertensos

AbstractBackground:Hypertension is a public health problem and increases the incidence of cardiovascular diseases.Objective:To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats.Methods:Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP).Results:Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H.Conclusion:One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

ResumoFundamento:A hipertensão é um problema de saúde pública e faz aumentar a incidência das doenças cardiovasculares.Objetivo:Avaliar os efeitos de uma sessão de exercício resistido sobre os mecanismos contráteis e relaxantes do músculo liso vascular em artéria mesentérica de ratos hipertensos induzidos por L-NAME.Métodos:Ratos Wistar foram divididos em três grupos: Controle (C), Hipertenso (H) e Hipertenso Exercitado (HE). A hipertensão foi induzida pela administração de 20 mg/kg de NG-nitro L-arginina metil éster (L-NAME) durante sete dias antes dos protocolos experimentais. O protocolo de exercício resistido consistiu em dez séries de dez repetições e intensidade de 40% de uma repetição máxima. A reatividade do músculo liso vascular foi avaliada através de curvas concentração-resposta para a fenilefrina (FEN), cloreto de potássio (KCl) e nitroprussiato de sódio (NPS).Resultados:Os ratos tratados com L-NAME apresentaram aumento (p < 0,001) da Pressão Arterial Sistólica (PAS), da Pressão Arterial Diastólica (PAD) e da Pressão Arterial Média (PAM) quando comparados ao período inicial da indução. Não foi observada diferença na sensibilidade da FEN entre os grupos H e HE. O exercício resistido agudo reduziu (p < 0,001) a resposta contrátil induzida pelo KCl nas concentrações de 40 e 60 mM do grupo HE quando comparado ao grupo H. Foi observado maior (p < 0,01) sensibilidade do músculo liso ao NPS no grupo HE quando comparado ao grupo H.Conclusão:Uma sessão de exercício resistido reduz as respostas contráteis induzidas pelo KCl, além de aumentar a sensibilidade do músculo liso ao NO em artéria mesentérica de ratos hipertensos.

A Case-Control study of the prevalence of neurological diseases in inflammatory bowel disease (IBD) / Um estudo de caso-controle da prevalência de doenças neurológicas na doença inflamatória intestinal (DII)

Neurological diseases are common in inflammatory bowel disease (IBD) patients, but their exact prevalence is unknown. Method We prospectively evaluated the presence of neurological disorders in 121 patients with IBD [51 with Crohn's disease (CD) and 70 with ulcerative colitis (UC)] and 50 controls (gastritis and dyspepsia) over 3 years. Results Our standard neurological evaluation (that included electrodiagnostic testing) revealed that CD patients were 7.4 times more likely to develop large-fiber neuropathy than controls (p = 0.045), 7.1 times more likely to develop any type of neuromuscular condition (p = 0.001) and 5.1 times more likely to develop autonomic complaints (p = 0.027). UC patients were 5 times more likely to develop large-fiber neuropathy (p = 0.027) and 3.1 times more likely to develop any type of neuromuscular condition (p = 0.015). Conclusion In summary, this is the first study to prospectively establish that both CD and UC patients are more prone to neuromuscular diseases than patients with gastritis and dyspepsia. .

Doenças neurológicas são comuns em pacientes com doença inflamatória intestinal (DII), mas sua prevalência exata é desconhecida. Métodos Nós estudamos prospectivamente a presença de distúrbios neurológicos em 121 pacientes com DII [51 com doença de Crohn (DC) e 70 com colite ulcerativa (RCU)] e 50 controles (gastrite e dispepsia) ao longo de 3 anos. Resultados A avaliação neurológica padronizada (que incluiu testes eletrodiagnósticos) demonstrou que pacientes com DC foram 7,4 vezes mais propensos a desenvolver neuropatias de fibras grossas do que os controles (p = 0,045), 7,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,001) e 5,1 vezes mais propensos a desenvolver queixas autonômicas (p = 0,027). Pacientes com RCU foram 5 vezes mais propensos de desenvolver neuropatia de fibras grossas (p = 0,027) e 3,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,015). Conclusão Em resumo, este é o primeiro estudo prospectivo a estabelecer que os pacientes tanto com DC quanto de RCU são mais propensos a doenças neuromusculares do que os pacientes com gastrite e dispepsia. .