Search results for " alpha-1"
showing 10 items of 36 documents
Stenosis coexists with compromised α1-adrenergic contractions in the ascending aorta of a mouse model of Williams-Beuren syndrome
2020
Williams-Beuren syndrome (WBS) is a rare disorder caused by a heterozygous deletion of 26-28 contiguous genes that affects the brain and cardiovascular system. Here, we investigated whether WBS affects aortic structure and function in the complete deletion (CD) mouse model harbouring the most common deletion found in WBS patients. Thoracic aortas from 3-4 months-old male CD mice and wild-type littermates were mounted in wire myographs or were processed for histomorphometrical analysis. Nitric oxide synthase (NOS) isoforms and oxidative stress levels were assessed. Ascending aortas from young adult CD mice showed moderate (50%) luminal stenosis, whereas endothelial function and oxidative str…
Cardiac and vascular alpha(1)-adrenoceptors in congestive heart failure: a systematic review
2020
As heart failure (HF) is a devastating health problem worldwide, a better understanding and the development of more effective therapeutic approaches are required. HF is characterized by sympathetic system activation which stimulates α- and β-adrenoceptors (ARs). The exposure of the cardiovascular system to the increased locally released and circulating levels of catecholamines leads to a well-described downregulation and desensitization of β-ARs. However, information on the role of α-AR is limited. We have performed a systematic literature review examining the role of both cardiac and vascular α1-ARs in HF using 5 databases for our search. All three α1-AR subtypes (α1A, α1B and α1D) are exp…
Complex regional pain syndrome:intradermal injection of phenylephrine evokes pain and hyperalgesia in a subgroup of patients with upregulated α1-adre…
2018
The aim of this study was to determine whether upregulated cutaneous expression of α1-adrenoceptors (α1-AR) is a source of pain in patients with complex regional pain syndrome (CRPS). Immunohistochemistry was used to identify α1-AR on nerve fibres and other targets in the affected and contralateral skin of 90 patients, and in skin samples from 38 pain-free controls. The distribution of α1-AR was compared between patients and controls, and among subgroups of patients defined by CRPS duration, limb temperature asymmetry, and diagnostic subtype (CRPS I vs CRPS II). In addition, α1-AR expression was investigated in relation to pain and pinprick hyperalgesia evoked by intradermal injection of th…
Topical prazosin attenuates sensitivity to tactile stimuli in patients with complex regional pain syndrome
2015
Background The sympathetic nervous system may play an important role in certain forms of chronic pain. The main aim of this study was to determine whether functional blockade of α1-adrenoceptors would alter sensitivity to cutaneous stimulation in patients with complex regional pain syndrome (CRPS). Methods and Results In an initial study, high-performance liquid chromatography-mass spectrometry of intradermal interstitial fluid collected from the forearms of three healthy individuals established that the α1-adrenoceptor antagonist prazosin penetrated the skin barrier when mixed in Lipoderm® cream base. Next, we found that application of this cream to the forearm of 10 healthy participants a…
Modulation of adrenergic responses of human vas deferens by K+ channel inhibitors.
2010
Objectives The present study was designed to evaluate the role of K + channels in the adrenergic responses of human vas deferens as well as the intervention of dihydropyridine-sensitive Ca 2+ channels on modulation of adrenergic responses by K + channel inhibitors. Methods Ring segments of the epididymal part of the vas deferens were taken from 32 elective vasectomies and mounted in organ baths for isometric recording of tension. We then studied the effects of K + channel blockers on neurogenic and norepinephrine-induced contractile responses. Results Addition of tetraethylammonium (TEA, 10 −3 M), a nonspecific K + channel blocker, or charybdotoxin (10 −7 M), a nonselective inhibitor of lar…
Functional evidence of inverse agonism in vascular smooth muscle
1996
1. In the present study, depletion of internal Ca2+ stores sensitive to noradrenaline (1 microM) in rat aorta, is the signal for the entry of extracellular Ca2+, not only to refill the stores but also, in our experimental conditions, to activate the contractile proteins. This induces an increase in the resting tone that constitutes, the first functional evidence of this Ca2+ entry. 2. The fact that methoxamine (100 microM) reproduces the same processes as noradrenaline but clonidine (1 microM) does not, indicates that alpha(1)-adrenoceptor activation is related to the increase in the resting tone observed after depletion of adrenoceptor-sensitive internal Ca2+-stores. 3. Benoxathian and WB …
A possible structural determinant of selectivity of boldine and derivatives for the alpha 1A-adrenoceptor subtype.
1996
1. The selectivity of action of boldine and the related aporphine alkaloids, predicentrine (9-O-methylboldine) and glaucine (2,9-O-dimethylboldine) and alpha 1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding in rat cerebral cortex. WB 4101 and benoxathian were used as selective alpha 1A-adrenoceptor antagonists. 2. In the competition experiments [3H]-prazosin (0.2 nM) binding was inhibited by WB 4101 and benoxathian. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components (pKi = 9.92 and 8.29 for WB 4101, 9.35 and 7.94 for benoxathian). The two antagonists recognized approximately 37% of the sites with h…
3-D image analysis of fluorescent drug binding
2004
Fluorescent ligands provide the means of studying receptors in whole tissues using confocal laser scanning microscopy and have advantages over antibody- or non-fluorescence-based method. Confocal microscopy provides large volumes of images to be measured. Histogram analysis of 3-D image volumes is proposed as a method of graphically displaying large amounts of volumetric image data to be quickly analyzed and compared. The fluorescent ligand BODIPY FL-prazosin (QAPB) was used in mouse aorta. Histogram analysis reports the amount of ligand-receptor binding under different conditions and the technique is sensitive enough to detect changes in receptor availability after antagonist incubation or…
Therapeutic Modulation of Urinary Bladder Function: Multiple Targets at Multiple Levels
2015
Storage dysfunction of the urinary bladder, specifically overactive bladder syndrome, is a condition that occurs frequently in the general population. Historically, pathophysiological and treatment concepts related to overactive bladder have focused on smooth muscle cells. Although these are the central effector, numerous anatomic structures are involved in their regulation, including the urothelium, afferent and efferent nerves, and the central nervous system. Each of these structures involves receptors for—and the urothelium itself also releases—many mediators. Moreover, hypoperfusion, hypertrophy, and fibrosis can affect bladder function. Established treatments such as muscarinic antago…
Halogenated derivatives of boldine with high selectivity for alpha1A-adrenoceptors in rat cerebral cortex.
1999
The selectivity of 3-nitrosoboldine and different halogenated derivatives of boldine (3-bromoboldine, 3,8-dibromoboldine and 3-chloroboldine) for alpha1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding in rat cerebral cortex. In the competition experiments [3H]-prazosin binding was inhibited completely by all the compounds tested. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components. The relative order of affinity and selectivity for alpha1A-adrenoceptors was 3-bromoboldine = 3,8-dibromoboldine = 3-chloroboldineboldine3-nitrosoboldine. The competition curves for 3-bromoboldine remained shallow and biph…