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International Journal of Molecular... Mar 2024Both the endothelial (eNOS) and the neuronal (nNOS) isoforms of constitutive Nitric Oxide Synthase have been implicated in vascular dysfunctions in Alzheimer's disease...
Both the endothelial (eNOS) and the neuronal (nNOS) isoforms of constitutive Nitric Oxide Synthase have been implicated in vascular dysfunctions in Alzheimer's disease (AD). We aimed to explore the relationship between amyloid pathology and NO dynamics by comparing the cerebrospinal fluid (CSF) levels of nNOS and eNOS of 8 healthy controls (HC) and 27 patients with a clinical diagnosis of Alzheimer's disease and isolated CSF amyloid changes, stratified according to APOE ε genotype (APOE ε3 = 13, APOE ε4 = 14). Moreover, we explored the associations between NOS isoforms, CSF AD biomarkers, age, sex, cognitive decline, and blood-brain barrier permeability. In our cohort, both eNOS and nNOS levels were increased in APOE ε3 with respect to HC and APOE ε4. CSF eNOS inversely correlated with CSF Amyloid-β42 selectively in carriers of APOE ε3; CSF nNOS was negatively associated with age and CSF p-tau only in the APOE ε4 subgroup. Increased eNOS could represent compensative vasodilation to face progressive Aβ-induced vasoconstriction in APOE ε3, while nNOS could represent the activation of NO-mediated plasticity strategies in the same group. Our results confirm previous findings that the APOE genotype is linked with different vascular responses to AD pathology.
Topics: Humans; Alzheimer Disease; Apolipoprotein E3; Apolipoprotein E4; Amyloidogenic Proteins; Genotype; Protein Isoforms
PubMed: 38612537
DOI: 10.3390/ijms25073725 -
Diagnostics (Basel, Switzerland) Mar 2024This study aimed to precisely investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers through adaptive optics...
This study aimed to precisely investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers through adaptive optics retinal camera (AO) measurement. We included healthy volunteers (11 men and 14 women) aged 20.6 ± 0.9. The heart rate (HR) and systolic and diastolic blood pressures (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the AO-rtx1 (Imagine Eyes, Orsay, France) without pupil dilation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Cardiovascular parameter results: After exercise, SBP, DBP, and HR changed significantly from 130.2 ± 13.2 to 159.7 ± 15.6 mm Hg, 81.2 ± 6.3 to 77.1 ± 8.2 mm Hg, and 80.8 ± 16.1 to 175.0 ± 6.2 bpm, respectively ( < 0.002). Retinal microcirculation analysis showed no significant decrease in LD, Wall 1 after exercise: from 96.0 ± 6.8 to 94.9 ± 6.7 ( = 0.258), from 11.0 ± 1.5 to 10.4 ± 1.5 ( = 0.107), respectively, and significant reduction in VD from 118.5 ± 8.3 to 115.9 ± 8.3 ( = 0.047), Wall 2 from 11.5 ± 1.0 to 10.7 ± 1.3 ( = 0.017), WLR from 0.234 ± 0.02 to 0.222 ± 0.010 ( = 0.046), WCSA from 3802.8 ± 577.6 to 3512.3 ± 535.3 ( = 0.016). The AO is a promising technique for investigating the effects of exercise on microcirculation, allowing for the tracking of changes throughout the observation. Intensive dynamic physical exertion increases blood pressure and heart rate and causes the vasoconstriction of small retinal arterioles due to the autoregulation mechanism.
PubMed: 38611623
DOI: 10.3390/diagnostics14070710 -
Foods (Basel, Switzerland) Mar 2024Hypertension is the crucial modifiable risk factor for cardiovascular diseases, and efforts to identify functional foods that are effective for hypertension control are...
Hypertension is the crucial modifiable risk factor for cardiovascular diseases, and efforts to identify functional foods that are effective for hypertension control are increasing. The nutgall tree (NT, Mill.) is used in traditional medicine and food because of its medicinal value. However, the role of NT in hypertension has not been investigated. Therefore, the hypotensive effect of NT leaf ethanol extract (NTE) was investigated in spontaneously hypertensive rats (SHRs). SHRs were allocated to three groups (control, 300, or 1000 mg/kg NTE), and blood pressure was measured before and after oral administration. Systolic and diastolic blood pressure significantly decreased in the NTE 1000 mg/kg group and was the lowest at 2 h after administration (-26.4 ± 10.3, -33.5 ± 9.8%, respectively). Daily NTE administration for five days also resulted in a similar effect. Further, the vasorelaxant effects and related mechanisms were investigated in the aortas of Sprague Dawley rats. NTE showed the dose-dependent blood-vessel-relaxing effect, and its mechanism involves the NO-sGC-cGMP pathway, activation of K channels, and reduction in the vasoconstrictive action of angiotensin II. Therefore, our study provides basic data indicating the potential use of NTE as a functional food for high blood pressure.
PubMed: 38611347
DOI: 10.3390/foods13071041 -
Journal of Clinical Medicine Mar 2024Percutaneous nephrolithotomy (PNL) poses a risk of hypothermia. Additionally, general anesthesia lowers the thresholds for shivering and vasoconstriction, which leads...
Percutaneous nephrolithotomy (PNL) poses a risk of hypothermia. Additionally, general anesthesia lowers the thresholds for shivering and vasoconstriction, which leads to dysfunction of central thermoregulation. Perioperative hypothermia is associated with adverse outcomes after surgery. In this study, we aimed to demonstrate that prewarming for 10 min can effectively prevent early hypothermia during PNL. A total of 68 patients scheduled for elective PNL were recruited to this study from January to June 2022, but two patients were excluded because of a change in the surgical plan. After randomization, patients in the prewarming group ( = 32) received warming using a forced-air warming device for 10 min in the preoperative area before being transferred to the operating room, while the controls ( = 34) did not. The incidence of hypothermia within the first hour after inducing general anesthesia was the primary outcome. Perioperative body temperatures and postoperative recovery findings were also evaluated. Early intraoperative hypothermia decreased significantly more in the prewarming group than in the control group (9.4% vs. 41.2%, = 0.003). Moreover, the net decrease in core body temperature during surgery was smaller in the prewarming group than in the control group (0.2 °C, vs. 0.5 °C, = 0.003). In addition, the prewarmed patients had a lower incidence of postoperative shivering and a shorter post-anesthesia-care unit (PACU) stay (12.5% vs. 35.3%, = 0.031; and 46 vs. 50 min, = 0.038, respectively). Prewarming for 10 min decreased early hypothermia, preserved intraoperative body temperature, and improved postoperative recovery in the PACU.
PubMed: 38610608
DOI: 10.3390/jcm13071843 -
Sensors (Basel, Switzerland) Mar 2024Radial pulse diagnosis is the most common method to examine the human health state in Traditional East Asian Medicine (TEAM). A cold stress-related suboptimal health...
Visualizing a Cold Stress-Specific Pulse Wave in Traditional Pulse Diagnosis ('Tight Pulse') Correlated with Vascular Changes in the Radial Artery Induced by a Cold Pressor Trial.
Radial pulse diagnosis is the most common method to examine the human health state in Traditional East Asian Medicine (TEAM). A cold stress-related suboptimal health state (subhealth) is often undetectable during routine medical examinations, however, it can be detected through the palpation of specific pulse waves, particularly a 'tight pulse', in TEAM. Therefore, this study examined a correlation between 'tight pulse' and vascular changes in the radial artery (RA) induced by a cold pressor trial (CPT). Twenty healthy subjects underwent sequentially control trial and CPT with room-temperature and ice-cold water, respectively, on the right forearm. The radial pulse and vascular changes were then examined on the left arm. The radial pulse scores for frequencies of 'tight pulse' with strong arterial tension increased after the CPT compared with the control trial. The pulse scores were reversely correlated with the RA thickness and volumes in ultrasonography, but not with changes in the systolic/diastolic blood pressure. The RA thickness-based vascular surface and three-dimensional images visualized a 'tight pulse' showing the vasoconstriction and bumpy-/rope-shaped vascular changes in the radial pulse diagnostic region after the CPT. These findings provide valuable insights into the potential integration of clinical radial pulse diagnosis with ultrasonography for cold-related subhealth.
Topics: Humans; Radial Artery; Traditional Pulse Diagnosis; Cold-Shock Response; Heart Rate; Cold Temperature
PubMed: 38610298
DOI: 10.3390/s24072086 -
Biomedicine & Pharmacotherapy =... May 2024During resolution of inflammation, specialized proresolving mediators (SPMs), including resolvins, are produced to restore tissue homeostasis. We hypothesized that there...
Resolvin D2 prevents vascular remodeling, hypercontractility and endothelial dysfunction in obese hypertensive mice through modulation of vascular and proinflammatory factors.
During resolution of inflammation, specialized proresolving mediators (SPMs), including resolvins, are produced to restore tissue homeostasis. We hypothesized that there might be a dysregulation of SPMs pathways in pathological vascular remodeling and that resolvin D2 (RvD2) might prevent vascular remodeling and contractile and endothelial dysfunction in a model of obesity and hypertension. In aortic samples of patients with or without abdominal aortic aneurysms (AAA), we evaluated gene expression of enzymes involved in SPMs synthesis (ALOXs), SPMs receptors and pro-inflammatory genes. In an experimental model of aortic dilation induced by high fat diet (HFD, 60%, eighteen weeks) and angiotensin II (AngII) infusion (four weeks), we studied the effect of RvD2 administration in aorta and small mesenteric arteries structure and function and markers of inflammation. In human macrophages we evaluated the effects of AngII and RvD2 in macrophages function and SPMs profile. In patients, we found positive correlations between AAA and obesity, and between AAA and expression of ALOX15, RvD2 receptor GPR18, and pro-inflammatory genes. There was an inverse correlation between the expression of aortic ALOX15 and AAA growth rate. In the mice model, RvD2 partially prevented the HFD plus AngII-induced obesity and adipose tissue inflammation, hypertension, aortic and mesenteric arteries remodeling, hypercontratility and endothelial dysfunction, and the expression of vascular proinflammatory markers and cell apoptosis. In human macrophages, RvD2 prevented AngII-induced impaired efferocytosis and switched SPMs profile. RvD2 might represent a novel protective strategy in preventing vascular damage associated to hypertension and obesity likely through effects in vascular and immune cells.
Topics: Animals; Male; Humans; Docosahexaenoic Acids; Hypertension; Mice, Inbred C57BL; Obesity; Vascular Remodeling; Mice; Endothelium, Vascular; Diet, High-Fat; Angiotensin II; Aortic Aneurysm, Abdominal; Inflammation Mediators; Mice, Obese; Vasoconstriction; Inflammation; Macrophages; Disease Models, Animal
PubMed: 38608525
DOI: 10.1016/j.biopha.2024.116564 -
The Journal of International Medical... Apr 2024This study examined the effects of sildenafil on acute pulmonary embolism (APE) using a rat model.
OBJECTIVE
This study examined the effects of sildenafil on acute pulmonary embolism (APE) using a rat model.
METHODS
Sprague-Dawley rats were randomly divided into the sham, pulmonary thromboembolism (PTE), and sildenafil groups. The sham and PTE groups received normal saline once daily gavage for 14 consecutive days, whereas the sildenafil group received sildenafil (0.5 mg/kg/day) once daily gavage for 14 consecutive days. Autologous emboli were prepared from blood samples collected from the left femoral artery of rats in each group on day 13, and autologous emboli were injected into the jugular vein cannula of rats in the PTE and sildenafil groups on day 14. Sham-treated rats received the same volume of saline. Right systolic ventricular pressure (RVSP) and mean pulmonary arterial pressure (MPAP) were used to assess pulmonary embolism, and western blotting and enzyme-linked immunosorbent assay were used to detect relevant markers.
RESULTS
The Rho kinase signaling pathway was significantly activated in rats with APE, and sildenafil significantly inhibited this activation.
CONCLUSIONS
Sildenafil protected against APE through inhibiting Rho kinase activity, thereby reducing pulmonary vasoconstriction and decreasing elevated pulmonary arterial pressure. These findings might provide new ideas for the clinical treatment of acute pulmonary thromboembolism.
Topics: Rats; Animals; Sildenafil Citrate; rho-Associated Kinases; Rats, Sprague-Dawley; Pulmonary Embolism; Hemodynamics; Hominidae; Pulmonary Artery
PubMed: 38603613
DOI: 10.1177/03000605241240938 -
Hypertension Research : Official... Jun 2024Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos....
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 10-10 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.
Topics: Animals; Humans; Cardiovascular Diseases; Extracellular Vesicles; Hemodynamics
PubMed: 38600279
DOI: 10.1038/s41440-024-01659-x -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Mar 2024To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.
OBJECTIVE
To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.
METHODS
SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes, and histological changes of the thoracic aorta were evaluated using HE staining. In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings, the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine (NE)- and KCl-induced constriction. The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester, indomethacin, zinc protoporphyrin Ⅸ, tetraethyl ammonium chloride, glibenclamide, barium chloride, Iberiotoxin, 4-aminopyridine, or TASK-1-IN-1. The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.
RESULTS
Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology. While not obviously affecting resting aortic rings with intact endothelium, asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE, but its effects differed between endothelium-intact and endothelium-denuded rings. In endothelium-intact aortic rings pretreated with indomethacin, ZnPP Ⅸ, barium chloride, glyburide, TASK-1-IN-1 and 4-aminopyridine, asiaticoside did not produce significant effect on NE-induced vasoconstriction, and tetraethylammonium, Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside. In KCland NE-treated rings, asiaticoside obviously inhibited CaCl-induced vascular contraction.
CONCLUSION
Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening, promoting nitric oxide release from endothelial cells and regulating Ca influx and outflow, thereby reducing systolic blood pressure in rats.
Topics: Rats; Animals; Aorta, Thoracic; Blood Pressure; Vasodilation; Endothelial Cells; Calcium; Calcium Chloride; Nitroarginine; Rats, Sprague-Dawley; 4-Aminopyridine; Indomethacin; Esters; Endothelium, Vascular; Dose-Response Relationship, Drug; Chlorides; Triterpenes; Barium Compounds
PubMed: 38597444
DOI: 10.12122/j.issn.1673-4254.2024.03.14 -
BioRxiv : the Preprint Server For... Mar 2024A thermoregulatory decline occurs with age due to changes in muscle mass, vasoconstriction, and metabolism that lowers core body temperature (Tc). Although lower Tc is a...
A thermoregulatory decline occurs with age due to changes in muscle mass, vasoconstriction, and metabolism that lowers core body temperature (Tc). Although lower Tc is a biomarker of successful aging, we have previously shown this worsens cognitive performance in the APP/PS1 mouse model of Alzheimer's disease (AD) [1]. We hypothesized that elevating Tc with thermotherapy would improve metabolism and cognition in APP/PS1 mice. From 6-12 months of age, male and female APP/PS1 and C57BL/6 mice were chronically housed at 23 or 30°C. At 12 months of age, mice were assayed for insulin sensitivity, glucose tolerance, and spatial cognition. Plasma, hippocampal, and peripheral (adipose, hepatic, and skeletal muscle) samples were procured postmortem and tissue-specific markers of amyloid accumulation, metabolism, and inflammation were assayed. Chronic 30°C exposure increased Tc in all groups except female APP/PS1 mice. All mice receiving thermotherapy had either improved glucose tolerance or insulin sensitivity, but the underlying processes responsible for these effects varied across sexes. In males, glucose regulation was influenced predominantly by hormonal signaling in plasma and skeletal muscle glucose transporter 4 expression, whereas in females, this was modulated at the tissue level. Thermotherapy improved spatial navigation in male C57BL/6 and APP/PS1 mice, with the later attributed to reduced hippocampal soluble amyloid-β (Aβ). Female APP/PS1 mice exhibited worse spatial memory recall after chronic thermotherapy. Together, the data highlights the metabolic benefits of passive thermotherapy with potential nonpharmacological management for some individuals with AD, and provides further evidence for the necessity of adopting personalized patient care.
PubMed: 38586039
DOI: 10.1101/2024.03.26.586836