Diet-induced dilated cardiomyopathy (DCM) in dogs has been linked to grain-free, pea-containing diets, possibly due to increased oligosaccharides. Since cross-sectional human studies indicate that heart failure is associated with decreased cerebral blood flow and cognitive decline, we explored whether a similar association could be detected in dogs. This study tested whether diet-induced cardiac impairment coincides with a lower index of cerebral blood flow and cognitive decline in dogs. Eight adult Beagles were fed four diets for 5 weeks each. A commercial dental diet was fed pre-study as a husbandry diet, followed by three test diets fed in a randomized crossover design: a grain-based diet formulated with rice flour (GB), grain-based diet with rice flour and 1% of the oligosaccharide raffinose (GB O), and a grain-free diet containing pea flour (GF). Cardiac function and brain blood flow were assessed using ultrasound, and cognitive function using a sand maze test. Ejection fraction was lower and left ventricular end-systolic volume was greater in dogs fed the GF and husbandry diets compared to the GB and GB O diets. End-diastolic velocity and conductance index were greater in basilar cerebral arteries, while resistive index was lower in dogs fed GF and husbandry diets. Sand maze retrieval times were slower for GF and husbandry diet fed dogs compared to the GB O diet. Thus, reduced ejection fraction was associated with lower cerebral vascular tone and cognitive function in dogs fed GF and husbandry diets. This study is suggestive of a novel link between diet, cardiac function and cognition in dogs.

Integrated experimental and theoretical approaches to microvascular transport and regulation.

Red light therapy is emerging as a potential non-pharmacological modulator of thrombosis and hemostasis. Photobiomodulation with red, near-infrared (NIR), and far-infrared (FIR) wavelengths has been shown to influence nitric oxide release, endothelial function, platelet activation, and vascular tone. These effects align with the components of Virchow's triad (i.e., endothelial dysfunction, stasis, and hypercoagulability), and ameliorate thromboinflammation. Experimental data indicate that photobiomodulation may be effective to reduce platelet aggregation, von Willebrand factor activity, and improve microvascular perfusion. However, controversy remains regarding whether observed benefits reflect active red/NIR effects or simply the exclusion of pro-thrombotic blue light. Limitations in tissue penetration, protocol standardization, and translational modeling pose challenges for clinical implementation. Despite these uncertainties, red light therapy offers promise in high-risk patients where conventional anticoagulation is limited by bleeding risk. Future studies must define optimal dosing parameters, clarify mechanistic pathways, and evaluate efficacy in randomized clinical trials to establish its role in contemporary thrombosis management.

Modulation of blood pressure by estrogen: A modeling analysis.

ARF6 controls VSMC phenotypic switching upon lipid stimulation to promote inflammatory signaling contributing to the progression of atherosclerosis.

Smooth muscle cell phenotypic modulation during atherosclerosis.

Carvedilol decreases hepatic vascular resistance by reducing fibrogenesis and reversing endothelial dysfunction in cirrhotic rats.

Apolipoprotein M: Structural Insights, Functional Roles and Therapeutic Approaches in Vascular Disease.

Endothelial-derived nitric oxide (·NO) is a key signaling molecule in the vascular system, exerting concentration-dependent control over critical cellular functions such as angiogenesis, vascular tone, and endothelial barrier integrity. Tools for achieving reversible, spatiotemporally resolved modulation of intracellular ·NO, without pharmacological or genetic manipulation, are currently lacking. Here, we present a light-activated, nanoparticle (NP)-based strategy enabling bidirectional control of endogenous ·NO in endothelial cells. Composite NPs, based on poly(3-hexylthiophene), P3HT, and poly(3,4-ethylene-dioxythiophene):poly(styrenesulfonate), PEDOT:PSS polymers, are efficiently internalized in human (HUVEC) and murine (H5V) endothelial cells. In dark, NP uptake induces a ROS-dependent, intracellular ·NO increase (+50% and +100% in HUVEC and H5V, respectively, vs. controls), a metabolic shift toward glycolysis and upregulation of both endothelial nitric oxide synthase(eNOS, +50%) and induced nitric oxide synthase (iNOS, +40%). NP photostimulation reverses this response, decreasing ·NO below basal levels, up to -40% in HUVEC and H5V, via ROS-mediated scavenging and iNOS downregulation (-40%), partially restoring oxidative phosphorylation metabolism. Importantly, the photoexcitation protocol is compatible with perspective in vivo use, in terms of source type (LEDs) and power density (6 mW/cm2). Our approach represents an innovative strategy for bidirectional endothelial ·NO modulation, providing new opportunities in the emerging field of photo-redox medicine.

Background: Preeclampsia significantly alters maternal hemodynamics and may influence responses to spinal anesthesia during cesarean delivery. Understanding these differences is crucial for optimizing anesthetic management and maternal safety. Methods: This prospective observational study compared hemodynamic responses to spinal anesthesia in 64 parturients (32 preeclamptic, 32 normotensive) undergoing elective cesarean sections at Lal Ded Hospital, Srinagar. Hemodynamic parameters including blood pressure, heart rate, and oxygen saturation were monitored at 12 time points over 120 minutes. Statistical analysis employed independent t-tests and chi-square tests. Results: Preeclamptic patients demonstrated significantly higher baseline blood pressure (SBP 162.53±14.65 vs 134.47±6.41 mmHg, p<0.001) but lower heart rate (99.34±13.92 vs 107.56±15.00 bpm, p=0.025). Following spinal anesthesia, preeclamptic women experienced more profound percentage decreases in blood pressure (SBP 47.7% vs 15.7%, DBP 51.3% vs 24.6%, MAP 49.9% vs 19.3%) with delayed nadir occurrence at 25 minutes versus 5 minutes. Vasopressor requirements were significantly higher in preeclamptic patients (84.4% vs 18.8%, p<0.001). Conclusion: Preeclamptic patients exhibit distinct hemodynamic responses to spinal anesthesia characterized by more pronounced blood pressure reductions, delayed nadirs, and increased vasopressor requirements despite elevated baseline vascular tone, necessitating individualized monitoring and management strategies.

Vascular toxicity is a growing concern in cancer patients receiving vascular endothelial growth factor inhibitor (VEGFi) therapy, posing a significant threat to patient prognosis. While the primary mechanism of VEGFi-induced vascular toxicity is linked to redox-sensitive reactions that disrupt vascular tone, leading to hypertension and endothelial dysfunction, the role of the renal-vascular axis remains underexplored. This review seeks to clarify the contribution of the renal-vascular axis to VEGFi-related toxicity, focusing on key mechanisms such as endothelial dysfunction, activation of the renin-angiotensin-aldosterone system, oxidative stress and disrupted glomerular filtration. The renal-vascular axis is essential for regulating blood pressure and vascular tone, and its dysfunction may amplify VEGFi-induced cardiovascular injury. By exploring the interplay between renal and vascular systems in this context, we identify novel cardiovascular biomarkers and therapeutic targets that could help mitigate the vascular toxicity of VEGFi therapy. Understanding these mechanisms is crucial for enhancing the cardiovascular safety of cancer treatments and improving patient outcomes.

Endothelial glycocalyx in perioperative medicine current understanding and future direction.

Background: Perivascular adipose tissue (PVAT) is emerging as a signi cant player in hypertension and vascular dysfunction. This review explores PVAT's role in maintaining vascular homeostasis, its dysfunction in hypertensive conditions, and the molecular mechanisms involved. Objective: To evaluate the contributions of PVAT to vascular health in normal and hypertensive states, and to assess current and potential therapeutic interventions targeting PVAT for hypertension management. Methods: A comprehensive review of recent research, including animal studies, clinical trials, and advanced imaging techniques, was conducted. Key areas of focus included PVAT's physiological functions, its role in hypertension-induced vascular dysfunction, molecular pathways involved, and therapeutic strategies. Results: PVAT regulates vascular tone through vasodilatory molecules like adiponectin, nitric oxide (NO), and hydrogen sulphide (H S). In hypertension, PVAT exhibits increased oxidative stress, in ammation, and adipokine imbalance, contributing to vascular dysfunction. Current therapeutic approaches include pharmacological treatments (ARBs, ACEIs), lifestyle modi cations, and emerging molecular therapies. Advanced imaging and technological advancements o er new insights and therapeutic targets. Targeting PVAT presents a promising strategy for hypertension management. Future research should focus on translating animal model ndings to human applications, exploring advanced imaging techniques, and identifying novel biomarkers and therapies.

Caveolae, 50-100 nm cholesterol-rich plasma membrane invaginations, serve as critical signaling hubs in vascular cells. These structures-scaffolded by caveolin proteins (CAV1, CAV2, CAV3) and regulated by Cavins-orchestrate membrane dynamics, mechanotransduction, and lipid trafficking in endothelial cells, smooth muscle cells, and macrophages. In vascular physiology, caveolae modulate vascular tone, regulate lipoprotein metabolism, and mediate mechanosensation. In pathology, caveolae are implicated in atherosclerosis, pulmonary hypertension, and diabetic vasculopathy. This review synthesizes advances in caveolae biology, highlighting their roles in vascular homeostasis and disease. We propose caveolae-targeted therapies as promising strategies for cardiovascular disorders, contingent on resolving context-dependent signaling complexity.

Hemorrhagic shock caused by trauma is one of the most important contributors to mortality in severely injured patients. Management traditionally includes hemorrhage control and aggressive fluid resuscitation. Severe hemorrhagic shock induces a state of antidiuretic hormone (vasopressin) deficiency, which exacerbates vasodilatory shock and refractory hypotension. Recent clinical trials and reviews emphasize the potential benefits of low-dose vasopressin supplementation during trauma resuscitation. Vasopressin can restore vascular tone by acting independently of the adrenergic system, improve renal perfusion, promote hemostasis, and reduce the volume of required blood product transfusions without increasing complications. In this study, we aim to review the effect of AVP in traumatic patients presenting with hemorrhagic shock. This review is formatted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Quantitative randomized and observational study designs that evaluated the administration of vasopressin in trauma and hemorrhagic shock will be considered for systematic review. Databases PubMed (NCBI), PubMed Central (NCBI), Embase (Ovid), Scopus (Elsevier), and ClinicalTrials.gov (NLM) were searched for articles from 2000 to September 2025. Cochrane Library (Wiley) is also reviewed for possible systematic reviews on the subject. Further articles are sought through forward and backward citation tracking of the articles with the highest impact, especially randomized trials. Two independent blinded reviewers will screen the remaining articles for eligibility and methodological quality. Two independent authors will extract the data to decrease errors and bias. For statistical analysis, effect sizes will be expressed as risk ratios or ORs for dichotomous data or weighted (or standardized) mean differences and 95% CIs for continuous data. CRD420251154486. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251154486.

Statins, originally developed as lipid-lowering agents, have effects that extend well beyond cholesterol. By altering inflammatory signaling, vascular tone, fibrogenesis, and immune regulation, they engage pathways that shape a wide range of gastrointestinal diseases. Human data now suggest that these biological actions carry clinical weight. In metabolic dysfunction-associated steatotic liver disease and its progressive form, metabolic dysfunction-associated steatohepatitis, alcohol-associated liver disease, and chronic viral hepatitis (HBV and HCV), statin exposure is safe and associated with slower disease progression, fewer episodes of decompensation, and lower incidence of hepatocellular carcinoma. Randomized studies in cirrhosis show reductions in portal pressure, with cohort data linking use to fewer variceal bleeds, ascites, and hepatic encephalopathy. In inflammatory bowel disease, large registries and pilot trials indicate reduced flares, lower corticosteroid requirements, and decreased need for surgery, with early biomarker evidence supporting an anti-inflammatory effect. Smaller studies hint at benefits in other gastrointestinal contexts, though the evidence remains fragmented. Across these populations, true hepatotoxicity is rare; risk of myopathy is modest and largely confined to advanced cirrhosis or drug-drug interactions. Collectively, these findings support cautious repurposing of statins in gastroenterology and underline the need for definitive randomized trials to resolve class effects, optimize dose and duration, and identify reliable biomarkers of response.

Pulmonary arterial hypertension (PAH) is a serious disorder, in which increased vascular tone is one of the critical hallmarks. Since beta arrestins (bArrs) have been shown to regulate smooth muscle tone in the airways, we investigated the function of bArr1 in the pulmonary vasculature. Here, we report that bArr1 is essential for maintaining normal pulmonary arterial tone. Specifically, pulmonary arteries from bArr1-/- mice exhibited reduced NO-dependent vasorelaxation due to impaired soluble guanylyl cyclase (sGC) activity, which was restored by the heme-independent sGC activator BAY58-2667. We identified bArr1 as a binding partner of sGC and the sGC heme reductase cytochrome b5 reductase (Cyb5r3), indicating that bArr1 is vital for sensitizing sGC to NO. Finally, mice with either ubiquitous or smooth muscle-specific bArr1 deficiency developed pulmonary hypertension (PH). These findings highlight the important role of bArr1 in regulating pulmonary vascular tone and propose it as a potential therapeutic target for the treatment of PH.

The transient receptor potential vanilloid 4 channel (TRPV4) is thought to play a pivotal role in pulmonary arterial circulation. The present study hypothesizes that TRPV4 activation increases nitric oxide (NO) release and activates calcium-activated potassium of intermediate conductance (KCa3.1) in pulmonary arteries. Pulmonary arteries were isolated from wild-type mice (wt) and mice deficient in KCa3.1 channels (Kcnn4-/-) and mounted for simultaneous NO concentration and relaxation measurements. Human small pulmonary arteries were isolated and mounted in microvascular myographs for isometric tension recordings. Acetylcholine-induced increases in NO and relaxation of pulmonary arteries were slightly decreased in pulmonary arteries from Kcnn4-/- versus wt mice. An activator of TRPV4 channels, GSK1016790A, increased NO and relaxation to the same degree in pulmonary arteries from wt and Kcnn4-/- mice. A blocker of TRPV4 channels, HC06704, inhibited increases in NO concentration with no effect on acetylcholine (ACh) relaxation in pulmonary arteries from wt mice, but blocked increases in NO concentration and relaxation in pulmonary arteries from Kcnn4-/- mice and responses to GSK1016790A in pulmonary arteries from wt and Kcnn4-/- mice. Concentration-dependent relaxations induced by an inhibitor of sarcoplasmic Ca-ATPase, cyclopiazonic acid, were blocked in the presence of an inhibitor of NO synthase and a blocker of KCa3.1 channels, TRAM-34, in pulmonary arteries from wt mice, but were unaltered in the presence of TRAM-34 in arteries from Kcnn4-/- mice, or the presence of a blocker of TRPV4 channels. In small human pulmonary arteries, ACh and sodium nitroprusside (SNP) induced concentration-dependent relaxations, blocked by endothelial cell removal, in the presence of an inhibitor of NO synthase and the KCa3.1 channel blocker TRAM-34. GSK1016790A induced relaxation of human pulmonary arteries with endothelium, but failed to relax arteries without endothelium. The findings suggest that TRPV4 channels are involved in endothelium-dependent relaxation and likely regulate pulmonary vascular tone by modulating NO release.

Background: Caveolin-1 (Cav-1) is a protein found in various forms and locations within cells and tissues throughout the body. Studying its structure and function provides valuable insights into key cellular processes such as growth, death, and cell signaling. This review synthesizes evidence from human studies and animal models to elucidate the complex role of Caveolin-1 (Cav-1) in regulating nitric oxide (NO) synthesis within the vasculature and perivascular adipose tissue (PVAT) during atherosclerosis. Cav-1 is a master regulator of endothelial NO synthase (eNOS), a relationship well-defined in rodent endothelial cells and cell lines. In humans, loss-of-function CAV1 mutations are linked to pulmonary arterial hypertension, suggesting a protective vascular role. Paradoxically, Cav-1 is upregulated in atherosclerotic plaques. Whether this represents a pathological process reducing NO bioavailability or a compensatory response remains unclear. Furthermore, the direct translation of the Cav-1/eNOS axis to PVAT—a metabolically active tissue expressing Cav-1—is not fully established outside of preclinical models. PVAT influences vascular tone and inflammation, potentially contributing to the paradoxical, stage-specific roles of Cav-1 in disease. Resolving these questions requires integrating human observational data with mechanistic insights from animal models to evaluate Cav-1 as a therapeutic target in vascular disease.

Management of neonates with hypoplastic left heart syndrome following the Norwood procedure seeks to optimize systemic oxygen delivery while maintaining an appropriate distribution between systemic and pulmonary blood flow. The objective of this study was to quantify actively circulating blood volume, total cardiac output, the pulmonary-to-systemic blood flow ratio (Qp/Qs), and vascular resistance indices at fractions of inspired oxygen (FiO2) of 0.21, 0.5, and 0.9 during the early postoperative period. Measurements were obtained in 16 neonates using an ultrasound dilution technique that determines hemodynamic variables from changes in blood ultrasound velocity following injection of isotonic saline (COstatus, Transonic Systems Inc.). An increase in the Qp/Qs ratio was observed with rising FiO2, which was associated with a reduction in systemic blood flow, while pulmonary blood flow remained statistically unchanged across the FiO2 levels studied. This pattern is consistent with the interpretation that pulmonary blood flow in this setting is mainly influenced by the mechanical properties of the right ventricle to pulmonary artery shunt rather than by FiO2 mediated changes in pulmonary vascular tone. Actively circulating volume index was reduced at baseline and decreased further with increasing FiO2 accompanied by an increase in systemic vascular resistance. These findings indicate that the early postoperative hemodynamics in neonates after the Norwood procedure are more responsive to alterations in systemic circulation than to modulation of pulmonary vascular tone. Therapeutic strategies targeting augmentation of circulating blood volume and reduction of systemic afterload warrant further investigation as potential approaches to optimize postoperative management in this population.