RESUMEN

Neuronal activation sequence information is essential for understanding brain functions. Extracting such timing information from blood-oxygenation-level-dependent functional magnetic resonance imaging (fMRI) signals is confounded by local cerebral vascular reactivity (CVR), which varies across brain locations. Thus, detecting neuronal synchrony as well as inferring inter-regional causal modulation using fMRI signals can be biased. Here we used fast fMRI measurements sampled at 10 Hz to measure the fMRI latency difference between visual and sensorimotor areas when participants engaged in a visuomotor task. The regional fMRI timing was calibrated by subtracting the CVR latency measured by a breath-holding task. After CVR calibration, the fMRI signal at the lateral geniculate nucleus (LGN) preceded that at the visual cortex by 496 ms, followed by the fMRI signal at the sensorimotor cortex with a latency of 464 ms. Sequential LGN, visual, and sensorimotor cortex activations were found in each participant after the CVR calibration. These inter-regional fMRI timing differences across and within participants were more closely related to the reaction time after the CVR calibration. Our results suggested the feasibility of mapping brain activity using fMRI with accuracy in hundreds of milliseconds.

Asunto(s)

RESUMEN

α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model. The rats were divided into four groups: Sham surgery (Sham), the two-kidneys-one-clip (2K1C) group, and groups treated with LA for 14 days (Sham-LA and 2K1C-LA). No changes were observed in the pattern of food, water intake, and urinary volume. The left/right kidney weight LKw/RKw ratio was significantly higher in 2K1C animals. LA treatment did not reverse the increase in cardiac mass. In relation to vascular reactivity, there was an increase in the potency of phenylephrine (PHE) curve in the hypertensive animals treated with LA compared to the 2K1C group and also compared to the Sham group. Vasorelaxation induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were not improved by treatment with LA. Urea and creatinine levels were not altered by the LA treatment. In conclusion, the morphological changes in the aorta and heart were not reversed; however, the treatment with LA mitigated the contraction increase induced by the 2K1C hypertension.

RESUMEN

BACKGROUND: Sepsis is a leading cause of mortality in intensive care units and vasoactive drugs are widely used in septic patients. The cardiovascular response of septic shock patients during resuscitation therapies and the relationship of the cardiovascular response and clinical outcome has not been clearly described. METHODS: We included adult patients admitted to the ICU with sepsis from Peking Union Medical College Hospital (internal), Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD). The Blood Pressure Response Index (BPRI) was defined as the ratio between the mean arterial pressure and the vasoactive-inotropic score. BRRI was compared with existing risk scores on predicting in-hospital death. The relationship between BPRI and in-hospital mortality was calculated. A XGBoost's machine learning model identified the features that influence short-term changes in BPRI. FINDINGS: There were 2139, 9455, and 4202 patients in the internal, MIMIC-IV and eICU-CRD cohorts, respectively. BPRI had a better AUROC for predicting in-hospital mortality than SOFA (0.78 vs. 0.73, p = 0.01) and APS (0.78 vs. 0.74, p = 0.03) in the internal cohort. The estimated odds ratio for death per unit decrease in BPRI was 1.32 (95% CI 1.20-1.45) when BPRI was below 7.1 vs. 0.99 (95% CI 0.97-1.01) when BPRI was above 7.1 in the internal cohort; similar relationships were found in MIMIC-IV and eICU-CRD. Respiratory support and latest cumulative 12-h fluid balance were intervention-related features influencing BPRI. INTERPRETATION: BPRI is an easy, rapid, precise indicator of the response of patients with septic shock to vasoactive drugs. It is a comparable and even better predictor of prognosis than SOFA and APS in sepsis and it is simpler and more convenient in use. The application of BPRI could help clinicians identify potentially at-risk patients and provide clues for treatment. FUNDING: Fundings for the Beijing Municipal Natural Science Foundation; the National High Level Hospital Clinical Research Funding; the CAMS Innovation Fund for Medical Sciences (CIFMS) from Chinese Academy of Medical Sciences and the National Key R&D Program of China, Ministry of Science and Technology of the People's Republic of China.

Asunto(s)

RESUMEN

Shock is characterized with vascular hyporesponsiveness to vasoconstrictors, thereby to cause refractory hypotension, insufficient tissue perfusion, and multiple organ dysfunction. The vascular hyporeactivity persisted even though norepinephrine and fluid resuscitation were administrated, it is of critical importance to find new potential target. Ion channels are crucial in the regulation of cell membrane potential and affect vasoconstriction and vasodilation. It has been demonstrated that many types of ion channels including K+ channels, Ca2+ permeable channels, and Na+ channels exist in vascular smooth muscle cells and endothelial cells, contributing to the regulation of vascular homeostasis and vasomotor function. An increasing number of studies suggested that the structural and functional alterations of ion channels located in arteries contribute to vascular hyporesponsiveness during shock, but the underlying mechanisms remained to be fully clarified. Therefore, the expression and functional changes in ion channels in arteries associated with shock are reviewed, to pave the way for further exploring the potential of ion channel-targeted compounds in treating refractory hypotension in shock.

Asunto(s)

RESUMEN

Per- and polyfluoroalkyl substances (PFAS) are pervasive environmental pollutants frequently detected in drinking water worldwide. Reports linking PFAS exposure to cardiovascular disease have increased significantly in recent years. Furthermore, women appear to be more susceptible to the adverse effects of PFAS. However, the potential role of ovaries in the increased vulnerability of females to PFAS-related health effects remains unknown. In this study, we investigated the impact of perfluorooctane sulfonate (PFOS), a prominent PFAS, on the cardiovascular function in female rats with intact ovaries and ovariectomized (OVX) females. Bilateral OVX or sham surgeries were performed in 8-week-old female SD rats. Following recovery from surgeries, the rats were given drinking water containing 50 µg/mL of PFOS for 3 weeks. Control groups received PFOS-free water. PFOS exposure significantly reduced body weight but increased blood pressure similarly in both intact and OVX rats. Echocardiography analysis revealed that PFOS exposure decreased cardiac output, end-systolic volume, and end-diastolic volume in intact but not OVX rats. Vascular function studies demonstrated that PFOS equally reduced endothelium-dependent and -independent relaxation responses in intact and OVX rats. The endothelium-independent contractile responses were more pronounced in both intact and OVX rats. eNOS protein levels were similarly decreased in both intact and OVX rats. In conclusion, PFOS affects cardiac function through hormone-dependent mechanisms, while vascular function is impaired independent of ovarian status, indicating an intricate interplay between PFOS exposure, ovarian status, and cardiovascular function.

RESUMEN

Background: B-type natriuretic peptide (BNP) coordinates endothelial homeostasis and remodeling, with endothelial dysfunction associated with cardiovascular mortality in the general population without heart failure. The objective of this study was to investigate the correlation between serum N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels and endothelial dysfunction among patients diagnosed with hypertension. Methods: This cross-sectional, single-center study included 90 patients with hypertension. An electrochemiluminescence immunoassay measured NT-pro-BNP levels, and a digital thermal monitoring device calculated a vascular reactivity index (VRI) as a measurement for endothelial function. In this study, VRI < 1.0 denoted poor vascular reactivity, 1.0 ≤ VRI < 2.0 indicated intermediate vascular reactivity, and a VRI ≥ 2.0 suggested good vascular reactivity. Results: Out of all the hypertensive patients, eight (8.9%) displayed poor vascular reactivity (VRI < 1.0), while 39 (43.3%) exhibited intermediate vascular reactivity (1.0 ≤ VRI < 2.0), leaving the remaining 43 patients demonstrating good vascular reactivity. Older age (p = 0.012) and elevated serum NT-pro-BNP levels (p < 0.001) were found to be associated with poorer vascular reactivity. Older age (r = -0.221, p = 0.036) and log-transformed serum levels of NT-pro-BNP (log-NT-pro-BNP, r = -0.505, p < 0.001) exhibited a negative correlation with VRI values in patients with hypertension. Following a multivariate linear regression test, serum log-NT-pro-BNP level ( ß = -0.505, adjusted R 2 change = 0.246, p < 0.001) emerged as being significantly and independently associated with VRI values among hypertensive patients. Conclusions: In patients with hypertension, there was a negative association observed between serum log-NT-pro-BNP levels and endothelial dysfunction determined by VRI values.

RESUMEN

PURPOSE: Velocity selective arterial spin labeling (VSASL) quantification assumes that the labeled bolus continuously moves into the imaging voxel during the post-labeling delay (PLD). Faster blood flow could lead to a bolus duration shorter than the applied PLD of VSASL and cause underestimation of cerebral blood flow (CBF). This study aims to evaluate the performance of velocity-selective inversion (VSI) prepared arterial spin labeling (ASL) with different PLDs and pseudo-continuous ASL (PCASL) for quantification of hypercapnia-induced cerebrovascular reactivity (CVR), using phase-contrast (PC) MRI as a global reference. METHODS: We compared CVR obtained by VSI-ASL with PLD of 1520 ms (VSASL-1520), 1000 ms (VSASL-1000), and 500 ms (VSASL-500), PCASL with PLD of 1800 ms (PCASL-1800), and PC MRI on eight healthy volunteers at two sessions. RESULTS: Compared with PC MRI, VSASL-1520 produced significantly lower global CVR values, while PCASL-1800, VSASL-1000, and VSASL-500 yielded more consistent results. The reduced CVR in VSASL-1520 was more pronounced in carotid territories including frontal and temporal lobes than in vertebral territories such as the occipital lobe. This is largely caused by the underestimated perfusion during hypercapnia due to the reduced bolus duration being less than the PLD. CONCLUSION: Although VSASL offers certain advantages over spatially selective ASL due to its reduced susceptibility to delayed ATT, this technique is prone to biases when the ATT is excessively short. Therefore, a short PLD should be employed for reliable perfusion and CVR quantification in populations or conditions with fast flow.

Asunto(s)

RESUMEN

Circulating 25-hydroxyvitamin D (25(OH)D) significantly influences endothelial function. This study assessed the correlation between serum 25(OH)D and endothelial function using the vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples from 102 T2DM participants and VRI were assessed. Patients were divided into three categories based on VRI: low (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0). Among these patients, 30 (29.4%) had poor, 39 (38.2%) had intermediate, and 33 (32.4%) exhibited good vascular reactivity. Higher serum fasting glucose (p = 0.019), glycated hemoglobin (p = 0.009), and urinary albumin-to-creatinine ratio (p = 0.006) were associated, while lower prevalence of hypertension (p = 0.029), lower systolic blood pressure (p = 0.027), lower diastolic blood pressure (p < 0.001), and lower circulation 25(OH)D levels (p < 0.001) were associated with poor vascular reactivity. Significant independent associations between diastolic blood pressure (p = 0.002) and serum 25(OH)D level (p < 0.001) and VRI were seen in T2DM patients according to multivariable forward stepwise linear regression analysis. Serum 25(OH)D positively correlated with VRI values, and lower levels of serum 25(OH)D were linked to endothelial dysfunction in T2DM patients.

Asunto(s)

RESUMEN

Introduction: Vasodilatation in response to NO is a fundamental response of the vasculature, and during aging, the vasculature is characterized by an increase in stiffness and decrease in sensitivity to NO mediated vasodilatation. Vascular tone is regulated by the activation of smooth muscle and nonmuscle (NM) myosin, which are regulated by the activities of myosin light chain kinase (MLCK) and MLC phosphatase. MLC phosphatase is a trimeric enzyme with a catalytic subunit, myosin targeting subunit (MYPT1) and 20 kDa subunit of unknown function. Alternative mRNA splicing produces LZ+/LZ- MYPT1 isoforms and the relative expression of LZ+/LZ- MYPT1 determines the sensitivity to NO mediated vasodilatation. This study tested the hypothesis that aging is associated with changes in LZ+ MYPT1 and NM myosin expression, which alter vascular reactivity. Methods: We determined MYPT1 and NM myosin expression, force and the sensitivity of both endothelial dependent and endothelial independent relaxation in tertiary mesenteric arteries of young (6mo) and elderly (24mo) Fischer344 rats. Results: The data demonstrate that aging is associated with a decrease in both the expression of NM myosin and force, but LZ+ MYPT expression and the sensitivity to both endothelial dependent and independent vasodilatation did not change. Further, smooth muscle cell hypertrophy increases the thickness of the medial layer of smooth muscle with aging. Discussion: The reduction of NM myosin may represent an aging associated compensatory mechanism to normalize the stiffness of resistance vessels in response to the increase in media thickness observed during aging.

RESUMEN

Selenium compounds exert their antioxidant activity mostly when the selenium atom is incorporated into selenoproteins. In our work, we tested the possibility that selenite itself interacts with thiols to form active species that have reducing properties. Therefore, we studied the reduction of 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazol-1-yloxy-3-oxide radical (•cPTIO), damage of plasmid DNA (pDNA), modulation of rat hemodynamic parameters and tension of isolated arteries induced by products of interaction of selenite with thiols. We found that the products of selenite interaction with thiols had significant reducing properties that could be attributed mainly to the selenide and that selenite had catalytic properties in the access of thiols. The potency of thiols to reduce •cPTIO in the interaction with selenite was cysteine > homocysteine > glutathione reduced > N-acetylcysteine. Thiol/selenite products cleaved pDNA, with superoxide dismutase enhancing these effects suggesting a positive involvement of superoxide anion in the process. The observed •cPTIO reduction and pDNA cleavage were significantly lower when selenomethionine was used instead of selenite. The products of glutathione/selenite interaction affected several hemodynamic parameters including rat blood pressure decrease. Notably, the products relaxed isolated mesenteric artery, which may explain the observed decrease in rat blood pressure. In conclusion, we found that the thiol/selenite interaction products exhibited significant reducing properties which can be used in further studies of the treatment of pathological conditions caused by oxidative stress. The results of decreased rat blood pressure and the tension of mesenteric artery may be perspective in studies focused on cardiovascular disease and their prevention.

RESUMEN

Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos. They have been shown to be involved in maintaining homoeostasis as well as playing a role in the development of pathology including hypertension and cardiovascular disease. It is estimated that there is 109-1010 circulating EVs/mL in the plasma of healthy individuals derived from various sources. While the effect of EVs on vascular haemodynamic parameters will be dependent on the details of the model studied, we systematically searched and summarized current literature to find patterns in how exogenously injected EVs affected vascular haemodynamics. Under homoeostatic conditions, evidence from wire and pressure myography data demonstrate that injecting isolated EVs derived from cell types found in blood and blood vessels resulted in the impairment of vasodilation in blood vessels ex vivo. Impaired vasodilation was also observed in rodents receiving intravenous injections of human plasma EVs from cardiovascular diseases including valvular heart disease, acute coronary syndrome, myocardial infarction and end stage renal disease. When EVs were derived from models of metabolic syndromes, such as diabetes, these EVs enhanced vasoconstriction responses in blood vessels ex vivo. There were fewer publications that assessed the effect of EVs in anaesthetised or conscious animals to confirm whether effects on the vasculature observed in ex vivo studies translated into alterations in vascular haemodynamics in vivo. In the available conscious animal studies, the in vivo data did not always align with the ex vivo data. This highlights the importance of in vivo work to determine the effects of EVs on the integrative vascular haemodynamics.

Asunto(s)

RESUMEN

Introduction: Continuous monitoring of the pressure reactivity index (PRx) provides an estimation of dynamic cerebral autoregulation (CA) at the bedside in traumatic brain injury (TBI) patients. Visualising the time-trend of PRx with a risk bar chart in ICM + software at the bedside allows for better real-time interpretability of the autoregulation status. When PRx>0.3 is sustained for long periods, typically of at least half an hour, the bar shows a pattern called "red solid line" (RSL). RSL was previously described to precede refractory intracranial hypertension and brain death. Research question: We aimed to describe pathophysiological changes in measured signals/parameters during RSL. Material and methods: Observation of time-trends of PRx, intracranial pressure, cerebral perfusion pressure, brain oxygenation and compensatory reserve of TBI patients with RSL. Results: Three pathophysiological patterns were identified: RSL precedes intracranial hypertension, RSL is preceded by intracranial hypertension, or RSL is preceded by brain hypoperfusion. In all cases, RSL was followed by death and the RSL onset was between 1 h and 1 day before the terminal event. Discussion and conclusion: RSL precedes death in intensive care and could represent a marker for terminal clinical deterioration in TBI patients. These findings warrant further investigations in larger cohorts to characterise pathophysiological mechanisms underlying the RSL pattern and whether RSL has a significant relationship with outcome after TBI.

RESUMEN

Impaired spinal cord vascular function contributes to numerous neurological pathologies, making it important to be able to noninvasively characterize these changes. Here, we propose a functional magnetic resonance imaging (fMRI)-based method to map spinal cord vascular reactivity (SCVR). We used a hypercapnic breath-holding task, monitored with end-tidal CO2 (PETCO2), to evoke a systemic vasodilatory response during concurrent blood oxygenation level-dependent (BOLD) fMRI. SCVR amplitude and hemodynamic delay were mapped at the group level in 27 healthy participants as proof-of-concept of the approach, and then in two highly-sampled participants to probe feasibility/stability of individual SCVR mapping. Across the group and the highly-sampled individuals, a strong ventral SCVR amplitude was initially observed without accounting for local regional variation in the timing of the vasodilatory response. Shifted breathing traces (PETCO2) were used to account for temporal differences in the vasodilatory response across the spinal cord, producing maps of SCVR delay. These delay maps reveal an earlier ventral and later dorsal response and demonstrate distinct gray matter regions concordant with territories of arterial supply. The SCVR fMRI methods described here enable robust mapping of spatiotemporal hemodynamic properties of the human spinal cord. This noninvasive approach has exciting potential to provide early insight into pathology-driven vascular changes in the cord, which may precede and predict future irreversible tissue damage and guide the treatment of several neurological pathologies involving the spine.

RESUMEN

BACKGROUND: Sepsis is a serious complication that occurs after trauma, burns, and infections, and it is an important cause of death in intensive care unit (ICU) patients. Despite many new measures being proposed for sepsis treatment, its mortality rate remains high; sepsis has become a serious threat to human health, and there is an urgent need to carry out in-depth clinical research related to sepsis. In recent years, it has been found that septic shock-induced vasoplegia is a result of vascular hyporesponsiveness to vasopressors. Therefore, this study intended to establish an objective formula related to vasoplegia that can be used to assess the prognosis of patients and guide clinical treatment. MATERIALS AND METHODS: A retrospective cohort study was conducted using data from 106 septic shock patients admitted to the ICU of Jining No. 1 People's Hospital from January 2020 to December 2022. The patients were divided into mortality and survival groups based on 28-day survival, and hemodynamics were monitored by the pulse index continuous cardiac output system. The dose and duration of vasopressors, major hemodynamic parameters, lactic acid (Lac) levels, and Sequential Organ Failure Assessment scores were recorded within 48 h of hospital admission. Multifactorial logistic regression was used to analyze the independent risk factors affecting the prognosis of patients, and the predictive value of the vascular response index (VRI) was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: The differences between the survival and mortality groups in terms of age, sex ratio, body weight, ICU length of stay, distribution of infection sites, underlying disease conditions, baseline Lac levels, and some hemodynamic parameters were not statistically significant (P > .05). The results of multifactorial logistic regression showed that the admission Acute Physiology and Chronic Health Evaluation II score, Lac level at 24 h of treatment, maximal vasoactive inotropic score at 24 h (VISmax24), maximal vasoactive inotropic score at 48 h (VISmax48), and VRI were independent risk factors affecting 28-day mortality. Within 48 h of receiving vasopressor therapy, the VRI was lower in the mortality group than in the survival group. The area under the ROC curve for the VRI was 0.86, and the best cutoff value of the VRI for predicting 28-day mortality was 32.50 (YI = 0.80), with a sensitivity of 0.90, a specificity of 0.90, and a better prediction of mortality than the other indicators. CONCLUSIONS: The VRI is a good predictor of mortality in patients with septic shock, and a lower VRI indicates more severe vasoplegia, poorer prognosis, and higher mortality in patients with septic shock.

Asunto(s)

RESUMEN

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their female offspring and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of Glyphosate-based herbicide (O-GBH) and controls (O-CON) rats at six months of age. Relaxation to acetylcholine was reduced in O-GBH than in O-CON. Acute Indomethacin and Apocynin increased relaxation to acetylcholine in O-GBH. The aorta from O-GBH was hyperactive to phenylephrine; the preincubation with N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in O-CON than O-GBH. TEMPOL similarly reduced phenylephrine response, and L-NAME prevented this effect. The TBARS and GSH levels were increased in O-GBH than in O-CON. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that oxidative stress parameters altered, and the current levels considered safe for exposure to Glyphosate deserve further investigation, especially in the female gender.

Asunto(s)

RESUMEN

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke.

Asunto(s)

RESUMEN

Background and purpose Cerebral haemodynamics and cognitive performance may be adversely affected in type 2 diabetes mellitus (T2DM). Previous studies reported reduced cerebral blood flow (CBF) and altered cerebrovascular reactivity (CVR) in T2DM. Yoga, an ancient holistic health approach, is known to be beneficial for T2DM. We hypothesized that yoga practice may alter CBF and the flow resistance in the middle cerebral artery (MCA) and improve cognition in T2DM. Our secondary objective was to explore the relationship between changes in cerebral haemodynamics and cognition in T2DM. Materials and methods Participants were randomly allotted into the yoga and control groups based on the eligibility criteria. One hour of yoga intervention specific to type 2 diabetes was provided to the yoga group for three months, while conventional treatment was provided to the control group. A transcranial Doppler was used to evaluate longitudinal changes in cerebral haemodynamics in MCA. A Corsi block tapping test was used to assess visio-spatial working memory. Results There were 75 participants recruited, of whom 38 participated in yoga and 37 participated in a control group. Both intention to treat and per protocol analysis showed significant results. At day 90, intention-to-treat analysis showed significant changes in CBF velocities (mean difference -10.85%, 95% CI (-13.26, -6.15), p<0.001), cerebral vasodilatory reserve (mean difference -0.23%, 95% CI (-0.43, -0.03), p=0.02) and cognition (mean difference -12.13%, 95% CI (-17.48, -6.78), p≤0.001). There was no between-group effect. Also, the correlation between the CBF and cognition did not show any significant results. Conclusion The three-month yoga intervention was associated with an improvement in cerebral hemodynamics. The study also revealed an improvement in visio-spatial working memory among patients with T2DM. The study did not show any correlation between the improvement in cerebral haemodynamics and working memory. We recommend larger and longer studies on yoga intervention for T2DM patients to evaluate whether such benefits are sustained and improve their quality of life.

RESUMEN

AIMS: To evaluate the effects of testosterone on endothelium-dependent vasodilation and oxidative stress in mesenteric resistance arteries. MAIN METHODS: Spontaneously hypertensive rats (SHR), aged 8 to 10 weeks, were divided into four groups: intact (SHAM), intact treated with testosterone (TTO; 3 mg/kg/day) via subcutaneous route (s.c.), intact treated with testosterone and anastrozole [aromatase enzyme inhibitor (TTO + ANA; 0.1 mg/kg/day, s.c.)] and intact treated with testosterone and finasteride [5 α-reductase enzyme inhibitor (TTO + FIN; 5 mg/kg/day, s.c.)] for four weeks. Concentration-response curves to acetylcholine (ACh, 0.1 nmol/L - 10 µmol/L) were obtained in mesenteric resistance arteries previously contracted with phenylephrine (PE, 3 µmol/L), before and after the use of selective inhibitors. Reactive oxygen species (ROS) levels were assessed in the vessels and the endothelium analyzed by scanning electron microscopy. KEY FINDINGS: TTO group showed a lower participation of nitric oxide (NO), increased oxidative stress, and participation of prostanoids and endothelium-dependent hyperpolarization (EDH), possibly to maintain the vasodilator response. Lower participation of NO and prostanoids, combined to an increased participation of EDH, were observed in the TTO + ANA group, in addition to higher levels of ROS and altered endothelial morphology. The vasodilation to ACh was impaired in TTO + FIN, along increased participation of NO, reduction of prostanoids, and greater EDH-dependent vasodilation. SIGNIFICANCE: Testosterone contributes to endothelial vasodilation by enhancing EDH through an increased participation of epoxyeicosatrienoic acids. While the decrease in NO appears to involve the participation of dihydrotestosterone, 17 ß-estradiol seems to stimulate the action of the NO pathway and prostanoids.

Asunto(s)

RESUMEN

Excessive fructose intake presents the major risk factor for metabolic cardiovascular disease. Perivascular adipose tissue (PVAT) is a metabolic tissue and possesses a paracrine function in regulating aortic reactivity. However, whether and how PVAT alters vascular function under fructose overconsumption remains largely unknown. In this study, male Sprague-Dawley rats (8 weeks old) were fed a 60% high fructose diet (HFD) for 12 weeks. Fasting blood sugar, insulin, and triglycerides were significantly increased by HFD intake. Plasma adiponectin was significantly enhanced in the HFD group. The expression of uncoupling protein 1 (UCP1) and mitochondrial mass were reduced in the aortic PVAT of the HFD group. Concurrently, the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM) were suppressed. Furthermore, decreased fusion proteins (OPA1, MFN1, and MFN2) were accompanied by increased fission proteins (FIS1 and phospho-DRP1). Notably, the upregulated α-smooth muscle actin (α-SMA) and osteocalcin in the PVAT were concurrent with the impaired reactivity of aortic contraction and relaxation. Coenzyme Q10 (Q, 10 mg/100 mL, 4 weeks) effectively reversed the aforementioned events induced by HFD. Together, these results suggested that the dysregulation of mitochondrial dynamics mediated HFD-triggered PVAT whitening to impair aortic reactivity. Fortunately, coenzyme Q10 treatment reversed HFD-induced PVAT whitening and aortic reactivity.

RESUMEN

OBJECTIVE: Placental vascular reactivity (PlVR) indicates the ability of the placental vasculature to match blood supply to fetal demand. Many pregnancy disorders alter the characteristics of PlVR, resulting in suboptimal oxygen delivery, although current understanding is limited by the lack of non-invasive, repeatable methods to measure PlVR in utero. Our objective was to quantify PlVR by measuring the placental response to transient changes in maternal carbon dioxide (CO2) using blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI). We hypothesized that PlVR will increase with gestational age to meet the changing demands of a growing fetus, and that PlVR will be driven by a maternal response to changes in CO2 concentration. METHODS: This was a cross-sectional study of 35 women with a healthy singleton pregnancy, of whom 31 were included in the analysis. The median gestational age was 32.6 (range, 22.6-38.4) weeks. Pregnant women were instructed to follow audiovisual breathing cues during a MRI scan. Maternal end-tidal CO2 (EtCO2) was measured concurrently with resting placental BOLD MRI for a total of 7-8 min. Preprocessing of magnetic resonance images consisted of manual delineation of placental anatomy and motion correction. In each placental voxel, vascular reactivity was computed using a coherence-weighted general linear model between MRI signal and EtCO2 stimulus. Global PlVR was computed as the mean of voxel-wise PlVR values across the placenta. RESULTS: PlVR, quantified by the placental response to induced, transient changes in maternal CO2, was consistently measured in utero using BOLD MRI. PlVR increased non-linearly with advancing gestational age (P < 0.001) and was higher on the fetal side of the placenta. PlVR was associated positively with fetal brain volume after accounting for gestational age. PlVR did not show any significant associations with maternal characteristics. CONCLUSIONS: We present, for the first time, a non-invasive paradigm to quantify PlVR in ongoing human pregnancies without the use of exogenous gases or contrast agents. Our findings suggest that PlVR is driven by a fetal response to changes in maternal CO2. Ease of translation to the clinical setting makes PlVR a promising biomarker for the identification and management of high-risk pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Asunto(s)