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1.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473847

RESUMO

The normal ageing process affects resistance arteries, leading to various functional and structural changes. Systolic hypertension is a common occurrence in human ageing, and it is associated with large artery stiffening, heightened pulsatility, small artery remodeling, and damage to critical microvascular structures. Starting from young adulthood, a progressive elevation in the mean arterial pressure is evidenced by clinical and epidemiological data as well as findings from animal models. The myogenic response, a protective mechanism for the microcirculation, may face disruptions during ageing. The dysregulation of calcium entry channels (L-type, T-type, and TRP channels), dysfunction in intracellular calcium storage and extrusion mechanisms, altered expression of potassium channels, and a change in smooth muscle calcium sensitization may contribute to the age-related dysregulation of myogenic tone. Flow-mediated vasodilation, a hallmark of endothelial function, is compromised in ageing. This endothelial dysfunction is related to increased oxidative stress, lower nitric oxide bioavailability, and a low-grade inflammatory response, further exacerbating vascular dysfunction. Resistance artery remodeling in ageing emerges as a hypertrophic response of the vessel wall that is typically observed in conjunction with outward remodeling (in normotension), or as inward hypertrophic remodeling (in hypertension). The remodeling process involves oxidative stress, inflammation, reorganization of actin cytoskeletal components, and extracellular matrix fiber proteins. Reactive oxygen species (ROS) signaling and chronic low-grade inflammation play substantial roles in age-related vascular dysfunction. Due to its role in the regulation of vascular tone and structural proteins, the RhoA/Rho-kinase pathway is an important target in age-related vascular dysfunction and diseases. Understanding the intricate interplay of these factors is crucial for developing targeted interventions to mitigate the consequences of ageing on resistance arteries and enhance the overall vascular health.


Assuntos
Hipertensão , Vasoconstrição , Animais , Humanos , Adulto Jovem , Adulto , Cálcio/metabolismo , Proteômica , Artérias/metabolismo , Envelhecimento , Inflamação
2.
Eur J Neurol ; 31(5): e16246, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38470001

RESUMO

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) may cause ischaemic stroke and intracranial haemorrhage. The aim of our study was to assess the frequency of the afore-mentioned outcomes. METHODS: We performed a PROSPERO-registered (CRD42022355704) systematic review and meta-analysis accessing PubMed until 7 November 2022. The inclusion criteria were: (1) original publication, (2) adult patients (≥18 years), (3) enrolling patients with PRES and/or RCVS, (4) English language and (5) outcome information. Outcomes were frequency of (1) ischaemic stroke and (2) intracranial haemorrhage, divided into subarachnoid haemorrhage (SAH) and intraparenchymal haemorrhage (IPH). The Cochrane Risk of Bias tool was used. RESULTS: We identified 848 studies and included 48 relevant studies after reviewing titles, abstracts and full text. We found 11 studies on RCVS (unselected patients), reporting on 2746 patients. Among the patients analysed, 15.9% (95% CI 9.6%-23.4%) had ischaemic stroke and 22.1% (95% CI 10%-39.6%) had intracranial haemorrhage. A further 20.3% (95% CI 11.2%-31.2%) had SAH and 6.7% (95% CI 3.6%-10.7%) had IPH. Furthermore, we found 28 studies on PRES (unselected patients), reporting on 1385 patients. Among the patients analysed, 11.2% (95% CI 7.9%-15%) had ischaemic stroke and 16.1% (95% CI 12.3%-20.3%) had intracranial haemorrhage. Further, 7% (95% CI 4.7%-9.9%) had SAH and 9.7% (95% CI 5.4%-15%) had IPH. CONCLUSIONS: Intracranial haemorrhage and ischaemic stroke are common outcomes in PRES and RCVS. The frequency reported in the individual studies varied considerably.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Síndrome da Leucoencefalopatia Posterior , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Adulto , Humanos , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Síndrome da Leucoencefalopatia Posterior/complicações , Síndrome da Leucoencefalopatia Posterior/epidemiologia , Vasoconstrição , Vasoespasmo Intracraniano/complicações , Vasoespasmo Intracraniano/epidemiologia , Hemorragias Intracranianas/complicações , Hemorragias Intracranianas/epidemiologia , AVC Isquêmico/complicações , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/epidemiologia
3.
Taiwan J Obstet Gynecol ; 63(2): 234-237, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38485321

RESUMO

OBJECTIVE: With the development of diagnostic imaging, a new clinical entity called reversible cerebral vasoconstriction syndrome (RCVS), which is considered to be a cause of secondary headache, has emerged. We herein present two cases of RCVS with different patterns of clinical progression. CASE REPORT: Case 1 occurred during labor, whereas case 2 occurred after delivery. Neither case presnted thunderclap headache at the onset of symptoms. Hypertensive disorders of pregnancy did not occur during the pregnancy or the puerperium in either case. Neurological symptoms following mild headache (Case 1: coma; Case 2: paralysis of the right extremities) were observed. CONCLUSION: Even when a patient has no risk factors for RCVS and had no severe headache, it is important not to miss any of the neurological symptoms. Magnetic resonance imaging (MRI) strongly supports the diagnosis, even during pregnancy. In addition, the diagnosis should always be reviewed while excluding eclampsia.


Assuntos
Transtornos Cerebrovasculares , Vasoconstrição , Gravidez , Feminino , Humanos , Imageamento por Ressonância Magnética , Período Pós-Parto , Cefaleia
4.
Addict Biol ; 29(3): e13385, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38488472

RESUMO

Alcohol consumption is popular worldwidely and closely associated with cardiovascular diseases. Influences of paternal preconception alcohol consumption on offspring cerebral arteries are largely unknown. Male rats were randomly given alcohol or water before being mated with alcohol-naive females to produce alcohol- and control-sired offspring. Middle cerebral artery (MCA) was tested with a Danish Myo Technology wire myograph, patch-clamp, IONOPTIX, immunofluorescence and quantitative PCR. Alcohol consumption enhanced angiotensin II (AngII)-mediated constriction in male offspring MCA mainly via AT1R. PD123,319 only augmented AngII-induced constriction in control offspring. AngII and Bay K8644 induced stronger intracellular calcium transient in vascular smooth muscle cells (VSMCs) from MCA of alcohol offspring. L-type voltage-dependent calcium channel (L-Ca2+ ) current at baseline and after AngII-stimulation was higher in VSMCs. Influence of large-conductance calcium-activated potassium channel (BKC a ) was lower. Caffeine induced stronger constriction and intracellular calcium release in alcohol offspring. Superoxide anion was higher in alcohol MCA than control. Tempol and thenoyltrifluoroacetone alleviated AngII-mediated contractions, while inhibition was significantly higher in alcohol group. The mitochondria were swollen in alcohol MCA. Despite lower Kcnma1 and Prkce expression, many genes expressions were higher in alcohol group. Hypoxia induced reactive oxygen species production and increased AT1R expression in control MCA and rat aorta smooth muscle cell line. In conclusion, this study firstly demonstrated paternal preconception alcohol potentiated AngII-mediated vasoconstriction in offspring MCA via ROS-AT1R. Alcohol consumption increased intracellular calcium via L-Ca2+ channel and endoplasmic reticulum and decreased BKCa function. The present study provided new information for male reproductive health and developmental origin of cerebrovascular diseases.


Assuntos
Angiotensina II , Vasoconstrição , Feminino , Ratos , Masculino , Animais , Angiotensina II/farmacologia , Angiotensina II/metabolismo , Cálcio/metabolismo , Artérias Cerebrais/metabolismo , Consumo de Bebidas Alcoólicas , Estresse Oxidativo
5.
PLoS One ; 19(3): e0295558, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38466700

RESUMO

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome of recurrent thunderclap headaches and reversible vasoconstriction of the cerebral arteries on neuroimaging within 3 months of onset. Initial non-contrast computed tomography (CT) can reveal abnormalities such as ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH) can be present in patients with RCVS and may delay diagnosis. AIMS: We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. We aimed to estimate the prevalence of imaging abnormalities on initial non-contrast CT head in adult patients with RCVS. DATA SOURCES & ELIGIBILITY CRITERIA: We searched electronic databases including MEDLINE, EMBASE, and the Cochrane Register of Clinical Trials from inception to August 2, 2022. Eligible studies included articles reporting the prevalence of non-contrast CT abnormalities on initial neuroimaging in patients with RCVS, aged 18 and older. Case series, observational studies and clinical trials were included. Data was extracted directly from included papers using a standardized data charting form. RESULTS: The search yielded 722 titles with duplicates removed. Twenty studies that included 379 patients with RCVS met inclusion criteria. We classified non-contrast CT abnormalities as either ischemic stroke, ICH, or SAH. We pooled prevalence data using a random effects model with the inverse-variance weighted method. The most common imaging finding was SAH with a pooled prevalence of 24% (95% CI:17%-33%), followed by ICH at 14% (95% CI:8%-22%), and ischemic stroke at 10% (95% CI:7%-14%). The pooled prevalence of any of these imaging abnormalities on initial non-contrast CT was 31% (95% CI:23%-40%). Risk of bias was moderate to very-high-risk for case-series and low-risk for observational studies. CONCLUSION: Our review demonstrates that one-third of patients with RCVS will have an abnormality on initial non-contrast CT head, including either an ischemic stroke, ICH, or SAH. These findings highlight the diagnostic challenges of RCVS imaging and contribute to our understanding of this disease.


Assuntos
Transtornos Cerebrovasculares , AVC Isquêmico , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Adulto , Humanos , Vasoconstrição , Prevalência , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/epidemiologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/epidemiologia , Hemorragia Subaracnóidea/diagnóstico , Tomografia Computadorizada por Raios X , Cefaleia
6.
J Surg Res ; 296: 497-506, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38325012

RESUMO

INTRODUCTION: The mechanism of post-traumatic brain injury (TBI) hypoxemia involves ventilation/perfusion mismatch and loss of pulmonary hypoxic vasoconstriction. Inhaled nitric oxide (iNO) has been studied as an adjunct treatment to avoid the use of high positive end-expiratory pressure and inspired oxygen in treatment-refractory hypoxia. We hypothesized that iNO treatment following TBI would improve systemic and cerebral oxygenation via improved matching of pulmonary perfusion and ventilation. METHODS: Thirteen human patients with isolated TBI were enrolled and randomized to receive either placebo or iNO with measured outcomes including pulmonary parameters, blood gas data, and intracranial pressure (ICP) /perfusion. To complement this study, a porcine model of TBI (including 10 swine) was utilized with measured outcomes of brain tissue blood flow and oxygenation, ventilator parameters, and blood gas data both after administration and following drug removal and clearance. RESULTS: There were no clinically significant changes in pulmonary parameters in either the human or porcine arm following administration of iNO when compared to either the placebo group (human arm) or the internal control (porcine arm). Analysis of pooled human data demonstrated the preservation of alveolar recruitment in TBI patients. There were no clinically significant changes in human ICP or cerebral perfusion pressure following iNO administration compared to controls. CONCLUSIONS: iNO had no significant effect on clinically relevant pulmonary parameters or ICPs following TBI in both human patients and a porcine model. The pressure-based recruitment of the human lungs following TBI was preserved. Further investigation will be needed to determine the degree of utility of iNO in the setting of hypoxia after polytrauma.


Assuntos
Lesões Encefálicas Traumáticas , Óxido Nítrico , Humanos , Animais , Suínos , Pulmão , Hipóxia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Vasoconstrição , Administração por Inalação
7.
Auton Neurosci ; 252: 103154, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38330594

RESUMO

INTRODUCTION: Autonomic dysreflexia (AD) is a potentially life-threatening consequence in high (above T6) spinal cord injury that involves multiple incompletely understood mechanisms. While peripheral arteriolar vasoconstriction, which controls systemic vascular resistance, is documented to be pronounced during AD, the pathophysiological neurovascular junction mechanisms of this vasoconstriction are undefined. One hypothesized mechanism is increased neuronal release of norepinephrine and co-transmitters. We tested this by examining the effects of blockade of pre-synaptic neural release of norepinephrine and co-transmitters on cutaneous vasoconstriction during AD, using a novel non-invasive technique; bretylium (BT) iontophoresis followed by skin blood flow measurements via laser doppler flowmetry (LDF). METHODS: Bretylium, a sympathetic neuronal blocking agent (blocks release of norepinephrine and co-transmitters) was applied iontophoretically to the skin of a sensate (arm) and insensate (leg) area in 8 males with motor complete tetraplegia. An nearby untreated site served as control (CON). Cutaneous vascular conductance (CVC) was measured (CVC = LDF/mean arterial pressure) at normotension before AD was elicited by bladder stimulation. The percent drop in CVC values from pre-AD vs. AD was compared among BT and CON sites in sensate and insensate areas. RESULTS: There was a significant effect of treatment but no significant effect of limb/sensation or interaction of limb x treatment on CVC. The percent drop in CVC between BT and CON treated sites was 25.7±1.75 vs. 39.4±0.87, respectively (P = 0.004). CONCLUSION: Bretylium attenuates, but does not fully abolish vasoconstriction during AD. This suggests release of norepinephrine and cotransmitters from cutaneous sympathetic nerves is involved in cutaneous vasoconstriction during AD.


Assuntos
Disreflexia Autonômica , Compostos de Bretílio , Vasoconstrição , Masculino , Humanos , Temperatura Cutânea , Pele/inervação , Norepinefrina/farmacologia , Neurotransmissores/farmacologia , Fluxo Sanguíneo Regional
8.
Stroke ; 55(4): 1113-1117, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38362763

RESUMO

Reversible cerebral vasoconstriction syndrome (RCVS) refers to segmental, multifocal constriction of intracranial arteries along with acute headache and resolves within weeks. It occurs more commonly in women, and 1 well-known manifestation of RCVS is postpartum angiopathy. Furthermore, the female sex is included in scoring systems designed to assist with diagnosing RCVS. Nonetheless, the literature is mixed regarding the true role of female and pregnancy-related factors in the pathophysiology of RCVS, and it is similarly unclear whether management of this disorder differs by sex. Given the association of RCVS with female sex and the importance of highlighting, recognizing, and managing stroke etiologies in women, herein, the author reviews what is currently known and unknown about the topic of RCVS in women.


Assuntos
Transtornos da Cefaleia Primários , Acidente Vascular Cerebral , Vasoespasmo Intracraniano , Gravidez , Humanos , Feminino , Vasoconstrição/fisiologia , Vasoespasmo Intracraniano/etiologia , Acidente Vascular Cerebral/diagnóstico , Cefaleia/etiologia , Transtornos da Cefaleia Primários/etiologia , Transtornos da Cefaleia Primários/complicações
9.
ACS Biomater Sci Eng ; 10(3): 1517-1529, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38377553

RESUMO

The etiology of diabetic nephropathy (DN) is complex, and the incidence is increasing year by year. The patient's kidney showed oxidative stress damage, increasing active oxygen species (ROS) content, and vasoconstriction. Due to poor drug solubility and low renal accumulation, the current treatment regimens have not effectively alleviated glomerulopathy and other kidney damage caused by DN. Therefore, it is of great significance to explore new treatment strategies and drug delivery systems. Here, we constructed an oral nanodelivery system (Tel/CAN@CS-DA) that reduced oxidative stress and vasoconstriction. Deoxycholic acid (DA)-modified nanoparticles entered into intestinal epithelial cells (Caco2 cells) via the bile acid biomimetic pathway, then escaped from the lysosomes and eventually spat out the cells, increasing the oral absorption of nanoparticles. Chitosan (CS) nanoparticles could achieve renal targeting through specific binding with a renal giant protein receptor and deliver drugs to renal tubule epithelial cells (HK-2 cells). In vitro studies also proved that telmisartan (Tel) and canagliflozin (CAN) effectively removed cellular reactive oxygen species (ROS) and reduced HK-2 cell apoptosis caused by high glucose. In the in vivo model induced by streptozotocin (STZ), the results showed that the nanosystem not only elevated AMPK protein expression, inhibited angiotensin II (Ang II) protein expression to effectively reduce oxidative stress level, dilated renal blood vessels but also reduced the degree of inflammation and fibrosis. Overall, Tel/CAN@CS-DA multifunctional oral nanosystem can effectively treat DN with low toxicity, which provides a new idea for the treatment of DN.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Animais , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células CACO-2 , Vasoconstrição , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Estresse Oxidativo , Telmisartan/farmacologia , Telmisartan/uso terapêutico , Absorção Intestinal
10.
Intensive Care Med ; 50(3): 459-462, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38358543
11.
J Appl Physiol (1985) ; 136(4): 853-863, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38385182

RESUMO

Ventilation-perfusion matching occurs passively and is also actively regulated through hypoxic pulmonary vasoconstriction (HPV). The extent of HPV activity in humans, particularly normal subjects, is uncertain. Current evaluation of HPV assesses changes in ventilation-perfusion relationships/pulmonary vascular resistance with hypoxia and is invasive, or unsuitable for patients because of safety concerns. We used a noninvasive imaging-based approach to quantify the pulmonary vascular response to oxygen as a metric of HPV by measuring perfusion changes between breathing 21% and 30%O2 using arterial spin labeling (ASL) MRI. We hypothesized that the differences between 21% and 30%O2 images reflecting HPV release would be 1) significantly greater than the differences without [Formula: see text] changes (e.g., 21-21% and 30-30%O2) and 2) negatively associated with ventilation-perfusion mismatch. Perfusion was quantified in the right lung in normoxia (baseline), after 15 min of 30% O2 breathing (hyperoxia) and 15 min normoxic recovery (recovery) in healthy subjects (7 M, 7 F; age = 41.4 ± 19.6 yr). Normalized, smoothed, and registered pairs of perfusion images were subtracted and the mean square difference (MSD) was calculated. Separately, regional alveolar ventilation and perfusion were quantified from specific ventilation, proton density, and ASL imaging; the spatial variance of ventilation-perfusion (σ2V̇a/Q̇) distributions was calculated. The O2-responsive MSD was reproducible (R2 = 0.94, P < 0.0001) and greater (0.16 ± 0.06, P < 0.0001) than that from subtracted images collected under the same [Formula: see text] (baseline = 0.09 ± 0.04, hyperoxia = 0.08 ± 0.04, recovery = 0.08 ± 0.03), which were not different from one another (P = 0.2). The O2-responsive MSD was correlated with σ2V̇a/Q̇ (R2 = 0.47, P = 0.007). These data suggest that active HPV optimizes ventilation-perfusion matching in normal subjects. This noninvasive approach could be applied to patients with different disease phenotypes to assess HPV and ventilation-perfusion mismatch.NEW & NOTEWORTHY We developed a new proton MRI method to noninvasively quantify the pulmonary vascular response to oxygen. Using a hyperoxic stimulus to release HPV, we quantified the resulting redistribution of perfusion. The differences between normoxic and hyperoxic images were greater than those between images without [Formula: see text] changes and negatively correlated with ventilation-perfusion mismatch. This suggests that active HPV optimizes ventilation-perfusion matching in normal subjects. This approach is suitable for assessing patients with different disease phenotypes.


Assuntos
Hiperóxia , Infecções por Papillomavirus , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Oxigênio , Prótons , Circulação Pulmonar/fisiologia , Pulmão/fisiologia , Hipóxia , Vasoconstrição/fisiologia , Imageamento por Ressonância Magnética/métodos
12.
Am J Cardiol ; 217: 49-58, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38417650

RESUMO

Coronary endothelial dysfunction (CED) and coronary artery spasm (CAS) are causes of angina with no obstructive coronary arteries in patients. Both can be diagnosed by invasive coronary function testing (ICFT) using acetylcholine (ACh). This study aimed to evaluate the diagnostic yield of a 3-minute ACh infusion as compared with a 1-minute ACh bolus injection protocol in testing CED and CAS. We evaluated 220 consecutive patients with angina and no obstructive coronary arteries who underwent ICFT using continuous Doppler flow measurements. Per protocol, 110 patients were tested using 3-minute infusion, and thereafter 110 patients using 1-minute bolus injections, because of a protocol change. CED was defined as a <50% increase in coronary blood flow or any epicardial vasoconstriction in reaction to low-dose ACh and CAS according to the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria, both with and without T-wave abnormalities, in reaction to high dose ACh. The prevalence of CED was equal in both protocols (78% vs 79%, p = 0.869). Regarding the endotypes of CAS according to COVADIS, the equivocal endotype was diagnosed less often in the 3 vs 1-minute protocol (24% vs 44%, p = 0.004). Including T-wave abnormalities in the COVADIS criteria resulted in a similar diagnostic yield of both protocols. Hemodynamic changes from baseline to the low or high ACh doses were comparable between the protocols for each endotype. In conclusion, ICFT using 3-minute infusion or 1-minute bolus injections of ACh showed a similar diagnostic yield of CED. When using the COVADIS criteria, a difference in the equivocal diagnosis was observed. Including T-wave abnormalities as a diagnostic criterion reclassified equivocal test results into CAS and decreased this difference. For clinical practice, we recommend the inclusion of T-wave abnormalities as a diagnostic criterion for CAS and the 1-minute bolus protocol for practicality.


Assuntos
Acetilcolina , Vasoespasmo Coronário , Humanos , Angiografia Coronária , Vasoespasmo Coronário/diagnóstico , Vasoespasmo Coronário/epidemiologia , Vasoconstrição , Angina Pectoris , Vasos Coronários/diagnóstico por imagem
14.
Neurology ; 102(5): e209190, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38330283

RESUMO

A 54-year-old woman presented with headache and vasculopathy. She was treated for reversible cerebral vasoconstriction syndrome but continued to have clinicoradiographic decline with headache, seizures, systemic symptoms, and progression of vasculopathy on imaging. We present the diagnosis of a rare genetic disease with its various neurologic complications and systemic manifestations. Our case also illustrates the importance of differences in the metabolism of various antiseizure medications, recognition of which may avoid precipitating the disease.


Assuntos
Transtornos Cerebrovasculares , Vasoconstrição , Feminino , Humanos , Pessoa de Meia-Idade , Angiografia Cerebral , Cefaleia/etiologia , Raciocínio Clínico
15.
J Headache Pain ; 25(1): 17, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317074

RESUMO

BACKGROUND: The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates. METHODS: We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30 days) and remission (≥ 90 days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11). RESULTS: A total of 138 RCVS patients (mean age, 46.8 years ± 11.8; 128 women) and 42 HCs (mean age, 46.0 years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50-100 days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher. CONCLUSIONS: Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation.


Assuntos
Transtornos Cerebrovasculares , Vasoconstrição , Humanos , Feminino , Pessoa de Meia-Idade , Vasoconstrição/fisiologia , Imageamento por Ressonância Magnética , Artéria Cerebral Média , Cefaleia
16.
Science ; 383(6683): eade8064, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38330107

RESUMO

Penile erection is mediated by the corpora cavernosa, a trabecular-like vascular bed that enlarges upon vasodilation, but its regulation is not completely understood. Here, we show that perivascular fibroblasts in the corpora cavernosa support vasodilation by reducing norepinephrine availability. The effect on penile blood flow depends on the number of fibroblasts, which is regulated by erectile activity. Erection dynamically alters the positional arrangement of fibroblasts, temporarily down-regulating Notch signaling. Inhibition of Notch increases fibroblast numbers and consequently raises penile blood flow. Continuous Notch activation lowers fibroblast numbers and reduces penile blood perfusion. Recurrent erections stimulate fibroblast proliferation and limit vasoconstriction, whereas aging reduces the number of fibroblasts and lowers penile blood flow. Our findings reveal adaptive, erectile activity-dependent modulation of penile blood flow by fibroblasts.


Assuntos
Transportador 1 de Aminoácido Excitatório , Fibroblastos , Ereção Peniana , Pênis , Receptores Notch , Animais , Masculino , Camundongos , Circulação Sanguínea , Transportador 1 de Aminoácido Excitatório/metabolismo , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Ereção Peniana/fisiologia , Pênis/irrigação sanguínea , Pênis/fisiologia , Receptores Notch/metabolismo , Transdução de Sinais , Vasoconstrição , Vasodilatação
17.
Physiol Rep ; 12(4): e15944, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38366054

RESUMO

Maximal exercise capacity is reduced at altitude or during hypoxia at sea level. It has been suggested that this might reflect increased right ventricular afterload due to hypoxic pulmonary vasoconstriction. We have shown previously that the pulmonary vascular sensitivity to hypoxia is enhanced by sustained isocapnic hypoxia, and inhibited by intravenous iron. In this study, we tested the hypothesis that elevated pulmonary artery pressure contributes to exercise limitation during acute hypoxia. Twelve healthy volunteers performed incremental exercise tests to exhaustion breathing 12% oxygen, before and after sustained (8-h) isocapnic hypoxia at sea level. Intravenous iron sucrose (n = 6) or saline placebo (n = 6) was administered immediately before the sustained hypoxia. In the placebo group, there was a substantial (12.6 ± 1.5 mmHg) rise in systolic pulmonary artery pressure (SPAP) during sustained hypoxia, but no associated fall in maximal exercise capacity breathing 12% oxygen. In the iron group, the rise in SPAP during sustained hypoxia was markedly reduced (3.4 ± 1.0 mmHg). There was a small rise in maximal exercise capacity following sustained hypoxia within the iron group, but no overall effect of iron, compared with saline. These results do not support the hypothesis that elevated SPAP inhibits maximal exercise capacity during acute hypoxia in healthy volunteers.


Assuntos
Oxigênio , Vasoconstrição , Humanos , Tolerância ao Exercício , Voluntários Saudáveis , Artéria Pulmonar , Hipóxia , Altitude , Ferro/uso terapêutico
18.
STAR Protoc ; 5(1): 102845, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38294910

RESUMO

The isolated perfused kidney is a classic ex vivo preparation for studying renal physiology in general and vascular function. Here, we present a protocol for assessing myogenic tone in isolated mouse kidneys as well as vasodilatory and vasoconstrictive responses, expressed as perfusion pressure. We describe steps for pre-operative preparation, kidney and renal artery isolation, and connection of renal artery with glass cannula. We then detail how to measure pressure changes in perfused kidneys and the myogenic tone. For complete details on the use and execution of this protocol, please refer to Cui et al.1.


Assuntos
Rim , Vasoconstrição , Camundongos , Animais , Pressão Sanguínea/fisiologia , Perfusão
20.
Neurol Sci ; 45(1): 101-107, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37676373

RESUMO

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by transient constriction of cerebral arteries, leading to severe headache and potential complications. The association between RCVS and Guillain-Barre syndrome (GBS) is rare and poorly understood and warrants further investigation. METHODS: A detailed case of RCVS in a patient with GBS was presented, followed by a comprehensive literature review. PubMed, Embase, and Google Scholar were searched for relevant cases and studies. RESULTS: The case involved a 62-year-old woman with GBS who developed RCVS. The literature review identified three additional reported cases. RCVS in GBS primarily affected middle-aged women and presented with a variety of neurological symptoms. Neuroimaging showed reversible vasoconstriction in the cerebral arteries, along with other complications such as posterior reversible encephalopathy syndrome, subarachnoid hemorrhage, and infarcts. While the treatment for GBS consisted mainly of intravenous immunoglobulin, specific treatments for RCVS remain unclear. CONCLUSIONS: The coexistence of RCVS and GBS is a rare occurrence. RCVS in GBS may result from the disruption of cerebral vascular tone regulation, possibly influenced by GBS-related dysautonomia and consequent high blood pressure. Recognizing RCVS in GBS patients is critical for appropriate management.


Assuntos
Transtornos Cerebrovasculares , Síndrome de Guillain-Barré , Síndrome da Leucoencefalopatia Posterior , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Pessoa de Meia-Idade , Humanos , Feminino , Vasoconstrição/fisiologia , Síndrome de Guillain-Barré/complicações , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Transtornos Cerebrovasculares/complicações , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/complicações , Vasoespasmo Intracraniano/diagnóstico por imagem
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