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S Gasparini, M R Melo, G F Leite, P A Nascimento, G M F Andrade-Franzé, J V Menani, E Colombari
Chronic infusion of aldosterone into the 4th ventricle (4th V) induces robust daily sodium intake, whereas acute injection of aldosterone into the 4th V produces no sodium intake. The inhibitory mechanism of the lateral parabrachial nucleus (LPBN) restrains sodium intake induced by different natriorexigenic stimuli and might affect the acute response to aldosterone into the 4th V. In the present study, 1.8% NaCl and water intake was tested in rats treated with acute injections of aldosterone into the 4th V combined with the blockade of the inhibitory mechanisms with injections of moxonidine (α2 adrenergic/imidazoline agonist) or methysergide (a serotonergic antagonist) into the LPBN...
January 16, 2017: Neuroscience
Monique L Parkin, Kyungjoon Lim, Sandra L Burke, Geoffrey A Head
We investigated the effects of chronic subcutaneous treatment with centrally-acting antihypertensive agents moxonidine, rilmenidine, and clonidine on the baroreflex control of heart rate (HR) in conscious normotensive rabbits over 3 weeks. Infusions of phenylephrine and nitroprusside were performed at week 0 and at weeks 1 and 3 of treatment to determine mean arterial pressure (MAP)-HR baroreflex relationships. A second curve was performed after intravenous methscopolamine to determine the sympathetic baroreflex relationship...
2016: Frontiers in Physiology
Ágnes Fehér, Viktória E Tóth, Mahmoud Al-Khrasani, Mihály Balogh, Bernadette Lázár, Zsuzsanna Helyes, Klára Gyires, Zoltán S Zádori
Imidazoline receptors (IRs) have been recognized as promising targets in the treatment of numerous diseases; and moxonidine and rilmenidine, agonists of I1-IRs, are widely used as antihypertensive agents. Some evidence suggests that IR ligands may induce anti-inflammatory effects acting on I1-IRs or other molecular targets, which could be beneficial in patients with inflammatory bowel disease (IBD). On the other hand, several IR ligands may stimulate also alpha2-adrenoceptors, which were earlier shown to inhibit, but in more recent studies to rather aggravate colitis...
February 2017: Inflammopharmacology
Slavica Filipic, Milica Elek, Marija Popović, Katarina Nikolic, Danica Agbaba
Fast and simple hydrophilic interaction liquid chromatography (HILIC) method was developed and validated for the analysis of moxonidine and its four impurities (A, B, C, and D) in pharmaceutical dosage form. All experiments were performed on the Agilent Technologies 1200 high-performance liquid chromatography (HPLC) system using Zorbax RX-SIL, 250 mm × 4.6 mm, 5 μm column as stationary phase (T = 25°C, F = 1 mL/min, and λ = 255 nm), and mixture of acetonitrile and 40 mM ammonium formate buffer (pH 2...
2016: Journal of Analytical Methods in Chemistry
Carsten P Bramlage, Mina Nasiri-Sarvi, Joan Minguet, Peter Bramlage, Gerhard Anton Müller
BACKGROUND AND AIMS: Arterial hypertension is a major cause of death worldwide. For the most part, treatment for hypertension can be performed on an outpatient basis. However, some patients also require inpatient treatment, and the contributing factors for this remain unknown. Therefore, the primary objective of the present study was to determine which patient characteristics are associated with inpatient treatment for arterial hypertension. METHODS: Here, we conducted a mono-centric study of 103 hypertensive subjects, who were treated as inpatients in the Department of Nephrology and rheumatology of the university medical faculty of Göttingen...
October 24, 2016: BMC Research Notes
David John Webb
Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence...
September 2016: Journal of Hypertension
Suraj Kumar, Maninder Kansal, Sumit Kumar, Abhishek Goyal
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Luis E Cobos-Puc, Araceli Sánchez-López, David Centurión
This study shows that in spontaneously hypertensive rats (SHR) of 14-weeks-old, the sympathetically-induced, but not noradrenaline-induced tachycardic response are higher than age-matched Wistar normotensive rats. Furthermore, in SHR the sympathetically-induced tachycardic response was: (1) unaffected by moxonidine (3μg/kgmin); (2) partially inhibited by B-HT 933 (30μg/kgmin), both at the lowest doses; and (3) completely inhibited by the highest doses of B-HT 933 (100μg/kgmin), moxonidine (10μg/kgmin) or agmatine (1000 and 3000μg/kgmin) while the noradrenaline-induced tachycardic responses remained unaffected by the above compounds, except by 3000μg/kgmin agmatine...
November 15, 2016: European Journal of Pharmacology
Gláucia M F Andrade-Franzé, Silvia Gasparini, Laurival A De Luca, Patrícia M De Paula, Débora S A Colombari, Eduardo Colombari, Carina A F Andrade, José V Menani
Facilitatory and inhibitory mechanisms in the central nucleus of the amygdala (CeA) and the lateral parabrachial nucleus (LPBN), respectively, are important for the control of sodium and water intake. Here we investigated the importance of the opioid mechanisms in the CeA for water and 0.3M NaCl intake in euhydrated or hyperosmotic rats treated with injections of muscimol (GABAA agonist) or moxonidine (α2 adrenergic/imidazoline agonist) into the LPBN, respectively. Male Holtzman rats (n=4-8/group) with stainless steel cannulas implanted bilaterally in the CeA and in the LPBN were used...
January 1, 2017: Behavioural Brain Research
Holly Digne-Malcolm, Matthew C Frise, Keith L Dorrington
Though antihypertensive drugs have been in use for many decades, the mechanisms by which they act chronically to reduce blood pressure remain unclear. Over long periods, mean arterial blood pressure must match the perfusion pressure necessary for the kidney to achieve its role in eliminating the daily intake of salt and water. It follows that the kidney is the most likely target for the action of most effective antihypertensive agents used chronically in clinical practice today. Here we review the long-term renal actions of antihypertensive agents in human studies and find three different mechanisms of action for the drugs investigated...
2016: Frontiers in Physiology
G Andreeva, V Gorbunov, V Beloliperskaya, S Kukushkin, E Zvolinskaya, O Lerman
OBJECTIVE: The aim of study was to define relationships between psychological traits of patients with arterial hypertension (AH) and the antihypertensive drug effectiveness.(Figure is included in full-text article.) DESIGN AND METHOD: : We analyzed ambulatory blood pressure monitoring (ABPM) data of 275 patients with AH without serious concomitant diseases We used data base of several studies with the same design: 1) the washout period duration - 1-2 weeks; 2) initial ABPM session (SpaceLabs 90207) before treatment; 3) treatment with standard therapeutic doses (amlodipin, diltiazem, metoprolol, betaxolol, enalapril, moxonidin, lisinopril) with the addition of diuretic if needed; 4) psychological status assessment was performed by the psychological questionnaire "Minnesota Multiphase Personality Inventory"(MMPI) before and at the end of the treatment...
September 2016: Journal of Hypertension
Luiz M Oliveira, Thiago S Moreira, Fu-Shan Kuo, Daniel K Mulkey, Ana C Takakura
Norepinephrine (NE) is a potent modulator of breathing that can increase/decrease respiratory activity by α1-/α2-adrenergic receptor (AR) activation, respectively. The retrotrapezoid nucleus (RTN) is known to contribute to central chemoreception, inspiration, and active expiration. Here we investigate the sources of catecholaminergic inputs to the RTN and identify respiratory effects produced by activation of ARs in this region. By injecting the retrograde tracer Fluoro-Gold into the RTN, we identified back-labeled catecholaminergic neurons in the A7 region...
September 1, 2016: Journal of Neurophysiology
Benjamin Keller, Jesús A García-Sevilla
This in vivo study assessed the potential of the imidazoline receptor (IR) ligands moxonidine (selective I1-IR), BU224 (selective I2-IR) and LSL61122 (mixed I1/I2-IR) to dampen excitotoxic signalling induced by kainic acid (KA; 45 mg/kg) in the mouse brain (hippocampus and cerebral cortex). KA triggered a strong behavioural syndrome (seizures; maximal at 60-90 minutes) and sustained stimulation (at 72 hours with otherwise normal mouse behaviour) of pro-apoptotic c-Jun-N-terminal kinases (JNK) and calpain with increased cleavage of p35 into neurotoxic p25 (cyclin-dependent kinase 5 [Cdk5] activators) in mouse hippocampus...
September 2016: Journal of Psychopharmacology
K A Cabral, C A F Andrade
The lateral parabrachial nucleus (LPBN) exerts an important inhibitory influence for the control of sodium and water intake. However, the importance of LPBN on renal responses and cardiovascular changes during extracellular dehydration are still unknown. Here we investigated the effects of bilateral injections of moxonidine (alpha2-adrenergic and imidazoline receptor agonist) on renal and cardiovascular changes in fluid-depleted rats. Male Wistar rats (n=4-8 per group) with bilateral stainless steel guide-cannulas implanted into the LPBN were treated with subcutaneous furosemide (10mg/kg)+captopril (5mg/kg) to induce fluid depletion...
October 2016: Neuroscience Research
Shaimaa S El-Sayed, Mohamed N M Zakaria, Rasha H Abdel-Ghany, Abdel A Abdel-Rahman
Blunted cystathionine-γ lyase (CSE) activity (reduced endogenous H2S-level) is implicated in hypertension and myocardial dysfunction in diabetes. Here, we tested the hypothesis that CSE derived H2S mediates the cardiovascular protection conferred by the imidazoline I1 receptor agonist moxonidine in a diabetic rat model. We utilized streptozotocin (STZ; 55mg/kg i.p) to induce diabetes in male Wistar rats. Four weeks later, STZ-treated rats received vehicle, moxonidine (2 or 6mg/kg; gavage), CSE inhibitor DL-propargylglycine, (37...
July 15, 2016: European Journal of Pharmacology
Luis E Cobos-Puc, Hilda Aguayo-Morales, Yesenia Silva-Belmares, Maria A González-Zavala, David Centurión
Moxonidine centrally inhibits the sympathetic activity through the I1-imidazoline receptor and nitric oxide. In addition, inhibits the peripheral cardiac sympathetic outflow by α2-adrenoceptors/I1-imidazoline receptors, although the role of α2-adrenoceptor subtypes or nitric oxide in the cardiac sympatho-inhibition induced by moxonidine are unknown. Therefore, the cardiac sympatho-inhibition induced by moxonidine (10μg/kgmin) was evaluated before and after of the treatment with the following antagonists/inhibitor: (1) BRL 44408, (300μg/kg, α2A), imiloxan, (3000μg/kg, α2B), and JP-1302, (300μg/kg, α2C), in animals pretreated with AGN 192403 (3000μg/kg, I1 antagonist); (2) N(ω)-nitro-l-arginine methyl ester (l-NAME; 34, 100, and 340μg/kgmin); and (3) the combinations of the highest dose of l-NAME plus AGN 192403 or BRL 44408...
July 5, 2016: European Journal of Pharmacology
Yang-Kai Wang, Qiang Yu, Xing Tan, Zhao-Tang Wu, Ru-Wen Zhang, Ya-Hong Yang, Wen-Jun Yuan, Qi-Kuan Hu, Wei-Zhong Wang
OBJECTIVE: Centrally acting antihypertensive action of moxonidine is a result of activation of Imidazoline-1 receptor (I1R) in the rostral ventrolateral medulla (RVLM). Hypertension shows an increase in reactive oxygen species (ROS) in the RVLM. The present objective was to determine the phosphoinositide-3 kinase (PI3K) signaling pathway involved in the effect of moxonidine on ROS generation in the RVLM of spontaneously hypertensive rat (SHR). METHODS: Wistar-Kyoto rats and SHR received intracisternal infusion (2 weeks) of tested agents which were subjected to subsequent experiments...
May 2016: Journal of Hypertension
Thomas S Ray
The drug MDMA, commonly known as ecstasy, produces a specific and distinct open hearted mental state, which led to the creation of a new pharmacological class, "entactogens". Extensive literature on its mechanisms of action has come to characterize MDMA as a "messy" drug with multiple mechanisms, but the consensus is that the distinctive entactogenic effects arise from the release of neurotransmitters, primarily serotonin. I propose an alternative hypothesis: The entactogenic mental state is due to the simultaneous direct activation of imidazoline-1 (I1) and serotonin-2 (5-HT2) receptors by MDMA...
February 2016: Medical Hypotheses
Francesca Cagnoni, Maurizio Destro, Erika Bontempelli, Giovanni Locatelli, Dagmara Hering, Markus P Schlaich
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Overactivation of the sympathetic nervous system (SNS) plays an important role in the pathogenesis of comorbidities related to AF such as hypertension, congestive heart failure, obesity, insulin resistance, and obstructive sleep apnea. Methods that reduce sympathetic drive, such as centrally acting sympatho-inhibitory agents, have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF...
February 2016: Current Hypertension Reports
R Kh Khafizianova, I M Burykin
BACKGROUND: Adequate and rational pharmacotherapy is an important element of rehabilitation of patients with myocardial infarction. Orders of the Ministry of Health of the Russian Federation, domestic and international guidelines, and scientific publications - all contain a complete algorithm for rational pharmacotherapy [1, 2]. These documents are based on the principles of evidence-based medicine (EBM) and help practicing physicians to carry out individualized and rational pharmacotherapy...
2015: International Journal of Risk & Safety in Medicine
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