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Vascular pharmacology

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https://www.readbyqxmd.com/read/28219708/novel-technique-to-determine-the-pka-of-clonidine-at-prejunctional-%C3%AE-2-adrenoceptors-in-cardiac-and-vascular-sympathetic-transmission
#1
James A Angus, Pravin Rajasekaran, Christine E Wright
Analytical pharmacology draws heavily on the concept of equilibrium of agonist and silent antagonist concentrations competing at a specific receptor site. This condition breaks down in nerve transmission when transmitter release is inhibited by prejunctional α2-adrenoceptors activated by an agonist such as clonidine. We have developed a method that allows the agonist dissociation constant KA of clonidine to be determined in a robust isolated right atrial assay of mouse, rat and guinea pig. By applying low numbers of field pulses 1-4 to prevent autoinhibitory feedback, clonidine shifted the nerve pulse stimulation-tachycardia curves to the right...
February 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28217447/aging-related-erectile-dysfunction-potential-mechanism-to-halt-or-delay-its-onset
#2
REVIEW
Monica G Ferrini, Nestor F Gonzalez-Cadavid, Jacob Rajfer
Erectile dysfunction (ED) will visit every man at some time in his life. The age at when that knock on the door is heard is totally dependent on one's genetics as well as other extrinsic factors. Unlike guests who come for a visit and then leave, once ED shows up it tends to hang around forever. To add insult to injury, the longer ED hangs around, the worse it will get. It is estimated that by the time a man is in his 40's, he has about a 40% chance of having some form of ED and this prevalence increases about 10% per decade thereafter...
February 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28217390/management-of-aneurysmal-subarachnoid-hemorrhage-state-of-the-art-and-future-perspectives
#3
REVIEW
Giovanni Grasso, Concetta Alafaci, R Loch Macdonald
BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) accounts for 5% of strokes and carries a poor prognosis. It affects around 6 cases per 100,000 patient years occurring at a relatively young age. METHODS: Common risk factors are the same as for stroke, and only in a minority of the cases, genetic factors can be found. The overall mortality ranges from 32% to 67%, with 10-20% of patients with long-term dependence due to brain damage. An explosive headache is the most common reported symptom, although a wide spectrum of clinical disturbances can be the presenting symptoms...
2017: Surgical Neurology International
https://www.readbyqxmd.com/read/28214828/role-for-target-of-rapamycin-mtor-signal-pathway-in-regulating-neuronal-injury-after-intracerebral-hemorrhage
#4
Jie-Ping Wang, Meng-Yu Zhang
BACKGROUND/AIMS: Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR signal and its downstream products to brain injuries induced by intracerebral hemorrhage (ICH) in rats. METHODS: Western Blot analysis was employed to examine the protein expression of mTOR and its downstream pathway and Caspase-3...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213290/zd0947-a-sulphonylurea-receptor-modulator-detects-functional-sulphonylurea-receptor-subunits-in-murine-vascular-smooth-muscle-atp-sensitive-k-channels
#5
Tadashi Yamamoto, Kohei Takahara, Keiichiro Uchida, Noriyoshi Teramoto
In order to identify functional sulphonylurea receptor (SUR.x) subunits of native ATP-sensitive K(+) channels (KATP channels) in mouse portal vein, the effects of ZD0947, a SUR.x modulator, were investigated on spontaneous portal vein contractions, macroscopic membrane currents and unitary currents recorded (using patch-clamp techniques) in freshly dispersed mouse portal vein myocytes. Spontaneous contractions in mouse portal vein were reversibly reduced by ZD0947 in a concentration-dependent manner (Ki = 293nM)...
February 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28212190/endothelial-cell-disease-emerging-knowledge-from-cerebral-cavernous-malformations
#6
Maria Grazia Lampugnani, Matteo Malinverno, Elisabetta Dejana
PURPOSE OF REVIEW: Endothelial cells dysfunctions are crucial determinants of several human diseases. We review here the most recent reports on endothelial cell defects in cerebral cavernous malformations (CCMs), particularly focusing on adherens junctions. CCM is a vascular disease that affects specifically the venous microvessels of the central nervous system and which is caused by loss-of-function mutation in any one of the three CCM genes (CCM1, 2 or 3) in endothelial cells. The phenotypic result of these mutations are focal vascular malformations that are permeable and fragile causing neurological symptoms and occasionally haemorrhagic stroke...
February 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28211642/biomechanical-strain-exacerbates-inflammation-on-a-progeria-on-a-chip-model
#7
João Ribas, Yu Shrike Zhang, Patrícia R Pitrez, Jeroen Leijten, Mario Miscuglio, Jeroen Rouwkema, Mehmet Remzi Dokmeci, Xavier Nissan, Lino Ferreira, Ali Khademhosseini
Organ-on-a-chip platforms seek to recapitulate the complex microenvironment of human organs using miniaturized microfluidic devices. Besides modeling healthy organs, these devices have been used to model diseases, yielding new insights into pathophysiology. Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease showing accelerated vascular aging, leading to the death of patients due to cardiovascular diseases. HGPS targets primarily vascular cells, which reside in mechanically active tissues...
February 17, 2017: Small
https://www.readbyqxmd.com/read/28210071/update-on-the-medical-management-of-gastrointestinal-beh%C3%A3-et-s-disease
#8
REVIEW
Giuseppe Lopalco, Donato Rigante, Vincenzo Venerito, Claudia Fabiani, Rossella Franceschini, Michele Barone, Giovanni Lapadula, Mauro Galeazzi, Bruno Frediani, Florenzo Iannone, Luca Cantarini
Behçet's disease (BD) is a multisystemic disorder of unknown etiology mainly defined by recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis, all of which represent the "stigmata" of disease. However, many other organs including the vascular, neurological, musculoskeletal, and gastrointestinal systems can be affected. The gastrointestinal involvement in Behçet's disease (GIBD), along with the neurological and vascular ones, represents the most feared clinical manifestation of BD and shares many symptoms with inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28207868/acetylcholine-versus-cold-pressor-testing-for-evaluation-of-coronary-endothelial-function
#9
Ahmed AlBadri, Janet Wei, Puja K Mehta, Sofy Landes, John W Petersen, R David Anderson, Bruce Samuels, Babak Azarbal, Eileen M Handberg, Quanlin Li, Margo Minissian, Chrisandra Shufelt, Carl J Pepine, C Noel Bairey Merz
BACKGROUND: Assessment of coronary endothelial function with intracoronary acetylcholine (IC-Ach) provides diagnostic and prognostic data in patients with suspected coronary microvascular dysfunction (CMD), but is often not feasible due in part to the time and expertise needed for pharmacologic mixing. Cold pressor testing (CPT) is a simple and safe stimulus useful for either invasive or non-invasive endothelial function testing and myocardial perfusion imaging but has not been specifically evaluated among symptomatic women with signs of ischemic heart disease (IHD) who have no obstructive coronary artery disease (CAD)...
2017: PloS One
https://www.readbyqxmd.com/read/28201967/dipeptidyl-peptidase-4-inhibitor-induced-angioedema-an-overlooked-and-potentially-lethal-adverse-drug-reaction
#10
Susanne Irene Scott, Michelle Fog Andersen, Lise Aagaard, Christian Von Buchwald, Eva Rye Rasmussen
Introduction Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzyme-inhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl peptidase-4 inhibitors (gliptins) and angioedema. Dipeptidyl peptidase-4 inhibitors are anti-diabetic drugs used to improve glycaemic control. They, as a class effect, inadvertently affect the degradation of the vasoactive kinins bradykinin and substance P, both of which can cause angioedema due to vasodilatation and increase in vascular permeability in the capillaries...
February 14, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28193521/pharmacological-inhibition-of-magl-lipase-attenuates-experimental-colon-carcinogenesis
#11
Ester Pagano, Francesca Borrelli, Pierangelo Orlando, Barbara Romano, Martina Monti, Lucia Morbidelli, Gabriella Aviello, Roberta Imperatore, Raffaele Capasso, Fabiana Piscitelli, Lorena Buono, Vincenzo Di Marzo, Angelo A Izzo
Colorectal cancer (CRC) is a major health problem in Western countries. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) exerts antiproliferative actions in a number of tumoral cell lines, including CRC cells. Monoacylglycerol lipase (MAGL), a serine hydrolase that inactivates 2-AG, is highly expressed in aggressive human cancer cells. Here, we investigated the role of MAGL in experimental colon carcinogenesis. The role of MAGL was assessed in vivo by using the xenograft and the azoxymethane models of colon carcinogenesis; MAGL expression was evaluated by RT-PCR and immunohistochemistry; 2-AG levels were measured by liquid chromatography mass spectrometry; angiogenesis was evaluated in tumor tissues [by microvessel counting and by investigating the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) proteins] as well as in human umbilical vein endothelial cells (HUVEC); cyclin D1 was evaluated by RT-PCR...
February 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28192258/binding-and-functional-pharmacological-characteristics-of-gepant-type-antagonists-in-rat-brain-and-mesenteric-arteries
#12
Majid Sheykhzade, Nilofar Amandi, Monica Vidal Pla, Bahareh Abdolalizadeh, Anette Sams, Karin Warfvinge, Lars Edvinsson, Darryl S Pickering
AIM: The neuropeptide calcitonin gene-related peptide (CGRP) is found in afferent sensory nerve fibers innervating the resistance arteries and plays a pivotal role in a number of neurovascular diseases such as migraine and subarachnoid bleedings. The present study investigates the binding and antagonistic characteristics of small non-peptide CGRP receptor antagonists (i.e. gepants) in isolated rat brain and mesenteric resistance arteries. METHODS: The antagonistic behavior of gepants was investigated in isolated rat mesenteric arteries using a wire myograph setup while binding of gepants to CGRP receptors was investigated in rat brain membranes using a radioligand competitive binding assay...
February 10, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28190469/proanthocyanidins-from-vitis-vinifera-inhibit-oxidative-stress-induced-vascular-impairment-in-pulmonary-arteries-from-diabetic-rats
#13
Christian Pinna, Paolo Morazzoni, Angelo Sala
BACKGROUND: Vitis vinifera L. (grape seed extract) is a natural source of proanthocyanidins with antioxidant and free radical-scavenging activities. HYPOTHESIS: Grape seed extract supplementation may prevent vascular endothelium impairment associated with diabetes mellitus in rat pulmonary artery. STUDY DESIGN: We evaluated endothelial function of rat pulmonary artery ex-vivo at the intermediate stage (4 weeks) of streptozotocin (STZ)-induced diabetes mellitus...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28190454/somatic-map2k1-mutations-are-associated-with-extracranial-arteriovenous-malformation
#14
Javier A Couto, August Y Huang, Dennis J Konczyk, Jeremy A Goss, Steven J Fishman, John B Mulliken, Matthew L Warman, Arin K Greene
Arteriovenous malformation (AVM) is a fast-flow, congenital vascular anomaly that may arise anywhere in the body. AVMs typically progress, causing destruction of surrounding tissue and, sometimes, cardiac overload. AVMs are difficult to control; they often re-expand after embolization or resection, and pharmacologic therapy is unavailable. We studied extracranial AVMs in order to identify their biological basis. We performed whole-exome sequencing (WES) and whole-genome sequencing (WGS) on AVM tissue from affected individuals...
January 30, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28188022/interplay-between-hsp90-and-nrf2-pathways-in-diabetes-associated-atherosclerosis
#15
Iolanda Lazaro, Ainhoa Oguiza, Carlota Recio, Laura Lopez-Sanz, Susana Bernal, Jesus Egido, Carmen Gomez-Guerrero
INTRODUCTION: Oxidative stress and inflammation are determinant processes in the development of diabetic vascular complications. Heat shock protein 90 (HSP90) overexpression in atherosclerotic plaques plays a role in sustaining inflammatory mechanisms, and its specific inhibition prevents atherosclerosis. The present work investigates, in a mouse model of diabetes-driven atherosclerosis, whether atheroprotection by pharmacological HSP90 inhibition is accomplished by bolstering antioxidant defense mechanisms headed by nuclear factor erythroid-derived 2-like 2 (Nrf2)...
February 7, 2017: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/28181559/sirtuin1-protects-endothelial-caveolin-1-expression-and-preserves-endothelial-function-via-suppressing-mir-204-and-endoplasmic-reticulum-stress
#16
M Kassan, A Vikram, Y R Kim, Q Li, A Kassan, H H Patel, S Kumar, M Gabani, J Liu, J S Jacobs, K Irani
Sirtuin1 (Sirt1) is a class III histone deacetylase that regulates a variety of physiological processes, including endothelial function. Caveolin1 (Cav1) is also an important determinant of endothelial function. We asked if Sirt1 governs endothelial Cav1 and endothelial function by regulating miR-204 expression and endoplasmic reticulum (ER) stress. Knockdown of Sirt1 in endothelial cells, and in vivo deletion of endothelial Sirt1, induced endothelial ER stress and miR-204 expression, reduced Cav1, and impaired endothelium-dependent vasorelaxation...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179107/pro-inflammatory-immune-to-brain-signaling-is-involved-in-neuroendocrine-responses-to-acute-emotional-stress
#17
Jordi Serrats, Jan-Sebastian Grigoleit, Elena Alvarez-Salas, Paul E Sawchenko
Activation of the hypothalamo-pituitary-adrenal (HPA) axis by inflammatory stressors (e.g., bacterial lipopolysaccharide) is thought to involve vascular transduction of circulating cytokines, with perivascular macrophages (PVMs) along with endothelia, effecting activation of HPA control circuitry via inducible (cyclooxygenase-2- or COX-2- dependent) prostaglandin synthesis. To test the stressor-specificity of this mechanism, we examined whether ablation of PVMs or pharmacologic blockade of COX activity affected HPA responses to a representative emotional stressor, restraint...
February 4, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28178410/strategies-to-extend-thrombolytic-time-window-for-ischemic-stroke-treatment-an-unmet-clinical-need
#18
REVIEW
Ike Dela Peña, Cesar Borlongan, Guofang Shen, Willie Davis
To date, reperfusion with tissue plasminogen activator (tPA) remains the gold standard treatment for ischemic stroke. However, when tPA is given beyond 4.5 hours of stroke onset, deleterious effects of the drug ensue, especially, hemorrhagic transformation (HT), which causes the most significant morbidity and mortality in stroke patients. An important clinical problem at hand is to develop strategies that will enhance the therapeutic time window for tPA therapy and reduce the adverse effects (especially HT) of delayed tPA treatment...
January 2017: Journal of Stroke
https://www.readbyqxmd.com/read/28174096/retinal-biomarkers-provide-insight-into-cortical-pharmacology-and-disease
#19
REVIEW
Christine To Nguyen, Flora Hui, Jason Charng, Shajan Velaedan, Anna van Koeverden, Jeremiah Kh Lim, Zheng He, Vickie Hy Wong, Algis J Vingrys, Bang V Bui, Magnus Ivarsson
The retina is an easily accessible out-pouching of the central nervous system (CNS) and thus lends itself favourable to being a biomarker of the brain. More specifically, the presence of neuronal, vascular and blood-neural barrier parallels in the eye and brain coupled with fast and inexpensive methods to quantify retinal changes make ocular biomarkers an attractive option. This includes its utility as a biomarker for multiple cerebrovascular diseases as well as a drug pharmacology and safety biomarker for the CNS...
February 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28167639/therapeutic-restoration-of-endothelial-glycocalyx-in-sepsis
#20
Jong Wook Song, Joseph A Zullo, Dionysios Liveris, Matthew Dragovich, X Frank Zhang, Michael S Goligorsky
Endothelial glycocalyx (EG) is disintegrated during sepsis. We showed (Am J Pathol, 2016) that this occurs very early in the course of sepsis and its prevention improves survival of mice with sepsis. Here, we sought to investigate the possibility to pharmacologically accelerate the restoration of disintegrated EG in sepsis. We used a soilage injection model to induce polymicrobial sepsis in C57/BL6 mice and measured total body EG. En face aortic preparations were used for staining for markers of EG and atomic force microscopy (AFM) was used to measure EG in vitro...
February 6, 2017: Journal of Pharmacology and Experimental Therapeutics
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