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Oxidative Medicine and Cellular... 2021We explored the role of ROS in cold-induced vasoconstriction and corresponding mechanism.
PURPOSE
We explored the role of ROS in cold-induced vasoconstriction and corresponding mechanism.
METHODS
Three experiments were performed. First, we measured blood flow in human hands before and after cold exposure. Second, 24 mice were randomly divided into 3 groups: 8 mice received saline injection, 8 received subcutaneous Tempol injection, and 8 received intrathecal Tempol injection. After 30 min, we determined blood flow in the skin before and after cold exposure. Finally, we used Tempol, CCG-1423, and Go 6983 to pretreat HAVSMCs and HUVECs for 24 h. Then, cells in the corresponding groups were exposed to cold (6 h, 4°C). After cold exposure, the cytoskeleton was stained. Intracellular Ca and ROS levels were measured by flow cytometry and fluorescence microscopy. We measured protein expression via Western blotting.
RESULTS
In the first experiment, after cold exposure, maximum skin blood flow decreased to 118.4 ± 50.97 flux units. Then, Tempol or normal saline pretreatment did not change skin blood flow. Unlike intrathecal Tempol injection, subcutaneous Tempol injection increased skin blood flow after cold exposure. Finally, cold exposure for 6 h shrank the cells, making them narrower, and increased intracellular Ca and ROS levels in HUVECs and HAVSMCs. Tempol reduced cell shrinkage and decreased intracellular Ca levels. In addition, Tempol decreased intracellular ROS levels. Cold exposure increased RhoA, Rock1, p-MLC-2, ET-1, iNOS, and p-PKC expression and decreased eNOS expression. Tempol or CCG-1423 pretreatment decreased RhoA, Rock1, and p-MLC-2 levels in HAVSMCs. Furthermore, Tempol or Go 6983 pretreatment decreased ET-1, iNOS, and p-PKC expression and increased eNOS expression in HUVECs.
CONCLUSION
ROS mediate the vasoconstrictor response within the cold-induced vascular response, and ROS in blood vessel tissues rather than nerve fibers are involved in vasoconstriction via the ROS/RhoA/ROCK1 and ROS/PKC/ET-1 pathways in VSMCs and endothelial cells.
Topics: Adult; Animals; Cold Temperature; Female; Humans; Male; Mice; Reactive Oxygen Species; Vasoconstriction
PubMed: 34868457
DOI: 10.1155/2021/8578452 -
Revista Medica de Chile Jun 2023Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium... (Review)
Review
Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.
Topics: Humans; Hypertension, Pulmonary; Calcium Channels; Animals; Calcium Signaling; Calcium Channel Blockers; Signal Transduction; Pulmonary Artery; Vasoconstriction
PubMed: 38801384
DOI: 10.4067/s0034-98872023000600753 -
Acta Physiologica (Oxford, England) Feb 2018Sphingosine-1-phosphate (S1P) influences resistance vessel function and is implicated in renal pathological processes. Previous studies revealed that S1P evoked potent...
AIM
Sphingosine-1-phosphate (S1P) influences resistance vessel function and is implicated in renal pathological processes. Previous studies revealed that S1P evoked potent vasoconstriction of the pre-glomerular microvasculature, but the underlying mechanisms remain incompletely defined. We postulated that S1P-mediated pre-glomerular microvascular vasoconstriction involves activation of voltage-dependent L-type calcium channels (L-VDCC) and the rho/rho kinase pathway.
METHODS
Afferent arteriolar reactivity was assessed in vitro using the blood-perfused rat juxtamedullary nephron preparation, and diameter was measured during exposure to physiological and pharmacological agents.
RESULTS
Exogenous S1P (10 -10 mol L ) evoked concentration-dependent vasoconstriction of afferent arterioles. Superfusion with nifedipine, a L-VDCC blocker, increased arteriolar diameter by 39 ± 18% of baseline and significantly attenuated the S1P-induced vasoconstriction. Superfusion with the rho kinase inhibitor, Y-27632, increased diameter by 60 ± 12% of baseline and also significantly blunted vasoconstriction by S1P. Combined nifedipine and Y-27632 treatment significantly inhibited S1P-induced vasoconstriction over the entire concentration range tested. In contrast, depletion of intracellular Ca stores with the Ca -ATPase inhibitors, thapsigargin or cyclopiazonic acid, did not alter the S1P-mediated vasoconstrictor profile. Scavenging reactive oxygen species (ROS) or inhibition of nicotinamide adenine dinucleotide phosphate oxidase activity significantly attenuated S1P-mediated vasoconstriction.
CONCLUSION
Exogenous S1P elicits potent vasoconstriction of rat afferent arterioles. These data also demonstrate that S1P-mediated pre-glomerular vasoconstriction involves activation of L-VDCC, the rho/rho kinase pathway and ROS. Mobilization of Ca from intracellular stores is not required for S1P-mediated vasoconstriction. These studies reveal a potential role for S1P in the modulation of renal microvascular tone.
Topics: Animals; Arterioles; Kidney; Lysophospholipids; Male; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; Renal Circulation; Sphingosine; Vasoconstriction
PubMed: 28640982
DOI: 10.1111/apha.12913 -
Blood Sep 2020
Topics: Anemia, Sickle Cell; Asthma; Humans; Primary Dysautonomias; Vasoconstriction
PubMed: 32882017
DOI: 10.1182/blood.2020007070 -
Journal of Biomedical Optics Aug 2023Corticosteroids-commonly prescribed medications for skin diseases-inhibit the secretion of vasodilators, such as prostaglandin, thereby exerting anti-inflammatory action...
SIGNIFICANCE
Corticosteroids-commonly prescribed medications for skin diseases-inhibit the secretion of vasodilators, such as prostaglandin, thereby exerting anti-inflammatory action by constricting capillaries in the dermis. The effectiveness of corticosteroids is determined by the degree of vasoconstriction followed by skin whitening, namely, the blanching effect. However, the current method of observing the blanching effect indirectly evaluates the effects of corticosteroids.
AIM
In this study, we employed optical-resolution photoacoustic (PA) microscopy (OR-PAM) to directly visualize the blood vessels and quantitatively evaluate vasoconstriction.
APPROACH
Using OR-PAM, the vascular density in mice skin was monitored for 60 min after performing each experimental procedure for four groups, and the vasoconstriction was quantified. Volumetric PA data were segmented into the papillary dermis, reticular dermis, and hypodermis based on the vascular characteristics obtained through OR-PAM. The vasoconstrictive effect of each skin layer was quantified according to the dermatological treatment method.
RESULTS
In the case of corticosteroid topical application, vasoconstriction was observed in the papillary ( ) and reticular ( ) dermis. For corticosteroid subcutaneous injection, constriction was observed solely in the reticular ( ) dermis. In contrast, no vasoconstrictions were observed with nonsteroidal topical application.
CONCLUSIONS
Our results indicate that OR-PAM can quantitatively monitor the vasoconstriction induced by corticosteroids, thereby validating OR-PAMs potential as a practical evaluation tool for predicting the effectiveness of corticosteroids in dermatology.
Topics: Animals; Mice; Anti-Inflammatory Agents; Skin; Adrenal Cortex Hormones; Vasoconstriction; Spectrum Analysis; Photoacoustic Techniques
PubMed: 36844430
DOI: 10.1117/1.JBO.28.8.082805 -
Nature Communications Nov 2020Understanding the structure and function of vasculature in the brain requires us to monitor distributed hemodynamics at high spatial and temporal resolution in...
Understanding the structure and function of vasculature in the brain requires us to monitor distributed hemodynamics at high spatial and temporal resolution in three-dimensional (3D) volumes in vivo. Currently, a volumetric vasculature imaging method with sub-capillary spatial resolution and blood flow-resolving speed is lacking. Here, using two-photon laser scanning microscopy (TPLSM) with an axially extended Bessel focus, we capture volumetric hemodynamics in the awake mouse brain at a spatiotemporal resolution sufficient for measuring capillary size and blood flow. With Bessel TPLSM, the fluorescence signal of a vessel becomes proportional to its size, which enables convenient intensity-based analysis of vessel dilation and constriction dynamics in large volumes. We observe entrainment of vasodilation and vasoconstriction with pupil diameter and measure 3D blood flow at 99 volumes/second. Demonstrating high-throughput monitoring of hemodynamics in the awake brain, we expect Bessel TPLSM to make broad impacts on neurovasculature research.
Topics: Animals; Blood Flow Velocity; Brain; Cerebrovascular Circulation; Feasibility Studies; Intravital Microscopy; Mice; Microscopy, Confocal; Microscopy, Fluorescence, Multiphoton; Models, Animal; Pupil; Stereotaxic Techniques; Vasoconstriction; Vasodilation; Wakefulness
PubMed: 33243995
DOI: 10.1038/s41467-020-19851-1 -
BMJ Case Reports Jan 2020Stress is under-recognised as a potential causative factor for reversible cerebral vasoconstriction syndrome (RCVS). Here we present a case of RCVS occurring during a...
Stress is under-recognised as a potential causative factor for reversible cerebral vasoconstriction syndrome (RCVS). Here we present a case of RCVS occurring during a time of extreme emotional duress. A 46-year-old female patient with medical history of bipolar disorder developed a severe headache during her father's funeral. The following day she was discovered to have bilateral hemiparesis, aphasia, encephalopathy and was brought emergently to the hospital. Neuroimaging revealed a 33 mL left fronto-parietal haematoma with subarachnoid blood near the vertex bilaterally. She underwent craniotomy, haematoma evacuation and external ventricular drain placement. The patient received two cerebral angiograms, the first showing multifocal cerebral vasoconstriction and the second showing resolution of these changes. She improved significantly over the course of her 3-week hospitalisation and eventually made a full recovery, including the ability to speak fluently in six languages with no significant deficits other than hypersomnia; she now requires 10 hours of sleep each night as compared with 7 hours prior to her brain injury.
Topics: Cerebral Angiography; Cerebrospinal Fluid; Cerebrovascular Disorders; Female; Grief; Humans; Middle Aged; Vasoconstriction
PubMed: 31996381
DOI: 10.1136/bcr-2019-232204 -
Brain and Behavior Dec 2019With a combination of different sympathetic tests, we aimed to elucidate whether impairment of sympathetic function in Parkinson's disease (PD) is the consequence of a...
OBJECTIVE
With a combination of different sympathetic tests, we aimed to elucidate whether impairment of sympathetic function in Parkinson's disease (PD) is the consequence of a central or peripheral efferent dysfunction.
METHODS
Thirty-five patients with early-to-intermediate PD (median age: 63 years; IQR: 57-67 years; disease duration 1-9 years, 15 women) and 20 age- and sex-matched healthy controls (median age: 64.5 years; IQR: 58-68 years; 10 women) were recruited. Autonomic testing was performed in two subgroups and included the assessment of resting cardiovascular parameters, postprandial hypotension (PPH), orthostatic hypotension (OH), and vasoconstriction induced by intradermal microdialysis with different concentrations of norepinephrine (NE; 10 ; 10 ; 10 ; 10 ) and by cold through forehead cooling. We also used sympathetic multiunit microneurography (muscle sympathetic nerve activity; MSNA; burst frequency (BF): bursts per minute; burst incidence (BI): bursts per 100 heart beats) and evaluated the presence of phosphorylated α-synuclein deposits in skin innervation in biopsies from the thighs by immunohistohemistry.
RESULTS
Diastolic blood pressure was higher in the PD group at rest (p < .001) and during OH (F = 6.533; p = .022). Vasoconstriction induced by NE microdialysis and cold was unchanged in PD patients. MSNA was lower in PD patients than in controls (BF: p = .001; BI: p = .025). Phosphorylated α-synuclein deposits could be found only in PD patients.
CONCLUSION
We did not find indications for peripheral sympathetic nerve fiber dysfunction or adrenoreceptor sensitivity changes. The decreased MSNA argues in favor of central sympathetic impairment.
Topics: Blood Pressure Determination; Central Nervous System; Diagnostic Techniques, Neurological; Female; Heart Rate; Humans; Male; Middle Aged; Parkinson Disease; Peripheral Nervous System; Sympathetic Nervous System; Vasoconstriction
PubMed: 31691543
DOI: 10.1002/brb3.1463 -
Journal of Applied Physiology... Jul 2017Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of...
Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of sex have not been fully elucidated. Nitric oxide (NO) has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle, and estrogen modulates NO synthase (NOS) expression and NO bioavailability. Therefore NO-mediated inhibition of sympathetic vasoconstriction may be enhanced in females. Thus the purpose of the present study was to investigate the hypothesis that sympathetic vasoconstrictor responsiveness would be blunted and NO-mediated inhibition of sympathetic vasoconstriction would be enhanced in females compared with males. Male (M; = 8) and female (F; = 10) Sprague-Dawley rats were anesthetized and surgically instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NOS blockade [-nitro-l-arginine methyl ester (l-NAME), 10 mg/kg iv]. At rest, sympathetic vasoconstrictor responsiveness was augmented ( < 0.05) in female compared with male rats at 2 Hz [F: -33 ± 8% (SD); M: -26 ± 6%] but was not different at 5 Hz (F: -55 ± 7%; M: -47 ± 7%). During muscle contraction, evoked vasoconstriction was similar ( > 0.05) in females and males at 2 Hz (F: -12 ± 5%; M: -13 ± 5%) but was blunted ( < 0.05) in females compared with males at 5 Hz (F: -24 ± 5%; M: -34 ± 8%). l-NAME increased ( < 0.05) sympathetic vasoconstrictor responsiveness in both groups at rest and during contraction. Contraction-mediated inhibition of vasoconstriction (sympatholysis) was enhanced ( < 0.05) in females compared with males; however, sympatholysis was not different ( > 0.05) between males and females in the presence of NOS blockade, indicating that NO-mediated sympatholysis was augmented in female rats. These data suggest that sex modulates sympathetic vascular control in resting and contracting skeletal muscle and that a portion of the enhanced sympatholysis in female rats was NO dependent. Sex differences in the neurovascular regulation of blood pressure and vascular resistance have been documented. However, our understanding of the underlying mechanisms that mediate these differences is incomplete. The present study demonstrates that female rats have an enhanced capacity to inhibit sympathetic vasoconstriction during exercise (sympatholysis) and that NO mediates a portion of the enhanced sympatholysis.
Topics: Adrenergic Fibers; Animals; Female; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Sprague-Dawley; Sex Characteristics; Vasoconstriction; Vasoconstrictor Agents
PubMed: 28473610
DOI: 10.1152/japplphysiol.00139.2017 -
Physiological Research Jun 2018The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity... (Review)
Review
The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. Impaired vasodilator reactivity has been recognized as an early hemodynamic abnormality in obese patients, but also increased vasoconstrictor tone importantly contributes to their vascular damage. In particular, upregulation of the endothelin (ET)-1 system, consistently reported in these patients, might accelerate atherosclerosis and its complication, given the pro-inflammatory and mitogenic properties of ET-1. In recent years, a number of gut hormones, in addition to their role as modulators of food intake, energy balance, glucose and lipid metabolism, and insulin secretion and action, have demonstrated favorable vascular actions. They increase the bioavailability of vasodilator mediators like nitric oxide, but they have also been shown to inhibit the ET-1 system. These features make gut hormones promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant advantages. Therefore, there is real hope that better understanding of the properties of gut-derived substances might provide more effective therapies for the obesity-related cardiometabolic syndrome.
Topics: Anti-Obesity Agents; Diabetes Mellitus, Type 2; Endothelin-1; Gastrointestinal Hormones; Humans; Insulin Resistance; Obesity; Peptide Hormones; Vasoconstriction; Vasoconstrictor Agents
PubMed: 29947529
DOI: 10.33549/physiolres.933821