Hypertensive Vessels Research Articles

Abstract P346: Expansion of meningeal lymphatic vessels in DOCA-salt hypertension

The meningeal lymphatic system is critical for proper brain waste clearance and maintenance of the local meningeal neuroimmune niche. Meningeal lymphatic function is impaired during aging and neurodegenerative diseases and is associated with the development of cognitive impairment. There is a bidirectional communication between meningeal lymphatic function and dural T cells, whereby the drainage of T cells into the deep cervical lymph nodes depends on functional lymphatic vessels, and meningeal lymphatic function is itself modulated by T cell derived cytokines. We have previously shown that IL-17A producing T cells accumulate in the dura during deoxycorticosterone acetate (DOCA)-salt hypertension and contribute to the impairment of neurovascular coupling and cognitive function. However, the mechanisms by which these T cells accumulate in the dura remain to be determined. Here, we tested the hypothesis that the meningeal lymphatic vessels are impaired during DOCA-salt hypertension, thus contributing to dural T cell accumulation. 12-week old C57BL6 male mice were implanted with a s.c. DOCA pellet and received 0.9% NaCl in the drinking water for 21 days (n=4). Control mice underwent a sham surgery (n=4). Blood pressure was monitored by tail-cuff plethysmography. Meningeal lymphatic vessels were assessed by immunohistochemistry using the lymphatic vessel marker LYVE1. In a separate group of mice, we assessed meningeal lymphatic function by delivering Alexa647-Ovalbumin or IgG-RPE into the cisterna magna and measuring fluorescence in the deep cervical lymph nodes one hour after injection. DOCA-salt mice developed increased systolic blood pressure (control: 117.7 ± 4.9 vs DOCA: 141.5 ± 2.9mmHg). We observed no difference in the CD31+ dural sinus area between control and DOCA-salt (control: 11.482 ± 0.718 vs DOCA: 11.816 ± 0.662 mm 2 ). We found a significant increase in LYVE1+ area surrounding the dural sinuses in DOCA-salt (control: 0.508 ± 0.039 vs DOCA: 0.816 ± 0.105 mm 2 ; p=0.0329 by unpaired two-tailed t-test) and an increase in LYVE1+/CD31+ % area (control: 4.476 ± 0.462 vs DOCA: 6.840 ± 0.609 %; p=0.0213 by unpaired two-tailed t-test) which was not different between the sagittal sinus or the transverse sinus. Contrary to our hypothesis, our data suggests that the meningeal lymphatic vessels are expanded, not retracted, during DOCA-salt hypertension. The interaction between meningeal lymphatics and dura immunity in hypertension remains to be determined.

Optimization of pulmonary artery mechanical testing

Pulmonary arterial hypertension (PAH) is an incurable disease with mortality within 3 years in 28-55% of high-risk patients. The progression of PAH has been known to be associated with increased vascular stiffness and vascular remodeling. Recent studies have suggested that increased stiffness may in fact be a driver for some of the metabolic abnormalities observed during PAH. To gain more insights into this relationship, we need to quantify the differences in mechanical properties of healthy and hypertensive pulmonary arteries. The stress-strain relationship is the gold standard for the ex-vivo stiffness measurement of arteries. This is obtained by obtaining force vs. distension data by tensile testing and using sample dimensions, i.e. length, lumen diameter, and wall thickness, to calculate engineering stress and strain. While this approach is well-optimized for large muscular arteries, it has not been used to test pulmonary arteries as their thin walls and low basal tone make it challenging to make precise measurements of sample wall thickness and lumen diameter. Thus, the goals of this study were to: 1) establish a reliable protocol for rat pulmonary artery tensile testing and 2) quantify the differences in stiffness between hypertensive and healthy pulmonary arteries. First, a methodology to improve the fidelity of determining the lumen diameter and wall thickness was developed. Using this approach, we observed that the modulus was negatively correlated with the length of the vessel segment tested. This suggests that vessel length should be standardized to perform reliable comparisons between groups. Next, we performed tensile tensing on both control and hypertensive pulmonary arteries, after standardizing vessel segment lengths. We initially modeled this tensile testing data using a one-term exponential equation and we observed that intact hypertensive arteries were ~2.7 times stiffer than control arteries at low strain (strain = 0.8). Whereas at high strain (strain = 2.8) intact and decellularized hypertensive arteries were 20 and 29 times stiffer than control arteries respectively. To better capture the viscoelastic properties of both, the cellular and ECM components of the vessels we also fit the tensile testing data using a two-term exponential equation. Using this two-term exponential model, we observed that hypertensive vessels were 2.2 times stiffer than the controls at normal hoop stress (20 kPa), and at the hypertensive hoop stress (66 kPa) the diseased vessels showed less variability in stiffness as compared to the controls. These findings and the methods developed in this study will be helpful in conducting and analyzing experiments to investigate the relationship between changes in biomechanical signals and the progression of PAH. R01HL151530 (KS), R01HL126514 (LS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Immunomodulatory Activity of Cytokines in Hypertension: A Vascular Perspective.

Cytokines play a crucial role in the structure and function of blood vessels in hypertension. Hypertension damages blood vessels by mechanisms linked to shear forces, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, oxidative stress, and a proinflammatory milieu that lead to the generation of neoantigens and damage-associated molecular patterns, ultimately triggering the release of numerous cytokines. Damage-associated molecular patterns are recognized by PRRs (pattern recognition receptors) and activate inflammatory mechanisms in endothelial cells, smooth muscle cells, perivascular nerves, and perivascular adipose tissue. Activated vascular cells also release cytokines and express factors that attract macrophages, dendritic cells, and lymphocytes to the blood vessels. Activated and differentiated T cells into Th1, Th17, and Th22 in secondary lymphoid organs migrate to the vessels, releasing specific cytokines that further contribute to vascular dysfunction and remodeling. This chronic inflammation alters the profile of endothelial and smooth muscle cells, making them dysfunctional. Here, we provide an overview of how cytokines contribute to hypertension by impacting the vasculature. Furthermore, we explore clinical perspectives about the modulation of cytokines as a potential therapeutic intervention to specifically target hypertension-linked vascular dysfunction.

Effect of FEMOKLIM on the state of blood vessels in hypoestrogenemia and arterial hypertension

The article presents the results of duplex scanning of the common carotid arteries (CCA) and assessment of the structural and functional state of the vascular bed of 57 women with arterial hypertension (AH) with hypoestrogenemia. It was found that with hypertension with a reduced level of estradiol, the lumen of the OCA increases, the speed of blood flow in the carotid arteries decreases, which indicates vascular remodeling. In the studied patients, in every third case, an inertial type of vasomotor reaction is detected before treatment, which indicates the contribution of dishormonosis to the progression of hypertension due to the development of endothelial dysfunction. Combined therapy with phytoestrogens and ACE inhibitors improves the structural and functional characteristics of the vascular wall, reduces arterial stiffness. The drug Femoklim is a source of phytohormones, hormones of entomological origin and natural antioxidants, has a positive effect on the state of the vascular system, improves blood microcirculation, is a capillary protector, has a complex harmonizing effect on the body.

A multiscale computational model of arterial growth and remodeling including Notch signaling.

Blood vessels grow and remodel in response to mechanical stimuli. Many computational models capture this process phenomenologically, by assuming stress homeostasis, but this approach cannot unravel the underlying cellular mechanisms. Mechano-sensitive Notch signaling is well-known to be key in vascular development and homeostasis. Here, we present a multiscale framework coupling a constrained mixture model, capturing the mechanics and turnover of arterial constituents, to a cell-cell signaling model, describing Notch signaling dynamics among vascular smooth muscle cells (SMCs) as influenced by mechanical stimuli. Tissue turnover was regulated by both Notch activity, informed by in vitro data, and a phenomenological contribution, accounting for mechanisms other than Notch. This novel framework predicted changes in wall thickness and arterial composition in response to hypertension similar to previous in vivo data. The simulations suggested that Notch contributes to arterial growth in hypertension mainly by promoting SMC proliferation, while other mechanisms are needed to fully capture remodeling. The results also indicated that interventions to Notch, such as external Jagged ligands, can alter both the geometry and composition of hypertensive vessels, especially in the short term. Overall, our model enables a deeper analysis of the role of Notch and Notch interventions in arterial growth and remodeling and could be adopted to investigate therapeutic strategies and optimize vascular regeneration protocols.

Inducible co-stimulatory molecules participate in mesenteric vascular endothelial-mesenchymal transition and sclerosis of mesenteric vessels in spontaneously hypertensive rats

To investigate the correlation of inducible co-stimulatory molecules (ICOS) with mesenteric vascular endothelial- mesenchymal transition (EndMT) and sclerosis in spontaneously hypertensive rats (SHR). Twenty 4-week-old WKY rats and 20 SHRs of the same strain were both randomly divided into 4 groups for observation at 4, 6, 10 and 30 weeks of age. ICOS expression frequency in rat spleen CD4+T cells was analyzed using flow cytometry, and the expressions of ICOS, VE-cad, α-SMA and Col3 mRNA in rat mesentery were detected by RT-PCR. The distributions of ICOS, IL-17A and TGF-β in rat mesentery were detected by immunohistochemistry. The levels of IL-17A and TGF-β in rat plasma were measured using ELISA. The morphological changes of rat mesenteric vessels were observed with Masson staining. Spearman or Pearson correlation analyses were used to evaluate the correlation between ICOS expression and the expressions of the markers of vascular EndMT and sclerosis. Compared with the control WKY rats, the SHRs began to show significantly increased systolic blood pressure and ICOS expression frequency on CD4+T cells at 6 weeks of age (P < 0.05). In the SHRs, the mRNA and protein expressions of ICOS, α-SMA, Col3, IL-17A and TGF-β in the mesentery were significantly higher than those in control group (P < 0.05), while the mRNA and protein expressions of VE-cad started to reduce significantly at 10 weeks of age (P < 0.05). The plasma levels of IL-17A and TGF-β were significantly increased in SHRs since 6 weeks of age (P < 0.05) with progressive worsening of mesenteric vascular sclerosis (P < 0.05). ICOS mRNA and protein expression levels in the mesenteric tissues of SHRs began to show positive correlations with α-SMA and Col3 expression levels and the severity of vascular sclerosis at 6 weeks of age (P < 0.05) and a negative correlation with VE-cad expression level at 10 weeks (P < 0.05). ICOS play an important pathogenic role in EndMT and sclerosis of mesenteric vessels in essential hypertension by mediating related immune responses.

Evaluation of the effect of metabolic therapy on the state of blood vessels in estrogen deficiency and hypertension

The article presents the results of duplex scanning of the common carotid arteries (CCA) and assessment of the structural and functional state of the vascular bed women with arterial hypertension (AH) with hypoestrogenemia. It was found that in patients with hypertension with a reduced level of estradiol, there is an expansion of the lumen of the CCA, a decrease in the speed of blood flow in the carotid arteries of a rectilinear course, without hemodynamically significant stenoses, which indicates structural and functional changes in the vascular wall. In the studied patients, in almost every third case, an inertial type of vasomotor reaction is detected before treatment, which indicates the contribution of dishormonosis to the progression of hypertension due to an increase in the stiffness of the vascular wall and the development of endothelial dysfunction. Combination therapy with BioDihydroquercetin and ACE inhibitor improves the structural and functional characteristics of the vascular wall of the CCA, has a positive effect on endothelial dysfunction, reduces the stiffness of the vascular wall of the arteries compared with patients taking ACE inhibitor monotherapy. The drug BioDihydroquercetin, produced with trade mark “Baikal Legend”, is a natural antioxidant, capillaroprotector, strengthens blood vessels, improves blood microcirculation, and is recommended to slow down the aging process of the body.

Deteriorated Vascular Homeostasis in Hypertension: Experimental Evidence from Aorta, Brain, and Pancreatic Vasculature.

Hypertension, as a primary risk factor for many fatal disorders, is prevalent in the elderly. There is wide literature on hypertension dealing with its biological and/or biochemical aspects; however, limited research is available on the multifactorial nature of hypertension from a mechanobiological standpoint. This study intended to study in parallel histopathological alterations and deviated protein expressions with the mechanical behavior of the hypertensive tissues. The Goldblatt (2K1C) method was chosen for induction of renovascular hypertension in rabbits. The microstructural and immunohistological characteristics of the aortic, pancreatic, and brain vasculature were investigated. The mechanical properties of the aortic tissue were also evaluated using biaxial tensile tests. Our findings indicated severe hypertrophy of the hypertensive vessels and declined content of intact smooth muscle cells. Most of the collagen I content of the wall was compromised and less functional type III collagen was highly expressed. Reversed collagen I to collagen III ratio was the main contributor to the hypertrophic and less stiff hypertensive vessel walls. The multifactorial nature of hypertension is illustrated, and smooth muscle cell detachment is identified as the sign of described degenerative cascades all along the arterial tree.

Hinokitiol produces vasodilation in aortae from normal and angiotensin II- induced hypertensive rats via endothelial-dependent and independent pathways

Hinokitiol is a natural bioactive compound with numerous pharmacological properties. Here, we aimed to examine hinokitiol's effects on vascular relaxation. Cumulative relaxation responses to hinokitiol were assessed in isolated aortae from normotensive and angiotensin II-induced hypertensive rats in the presence and absence of selective inhibitors. Hinokitiol produced vasodilation of phenylephrine preconstricted aortae using both normotensive and hypertensive rats. In normotensive rats, hinokitiol's vasodilation was reduced by endothelial denudation and nitric oxide synthase (NOS), guanylate cyclase, and cyclooxygenase inhibition. Also, hinokitiol vasodilation was attenuated by β-receptors, adenylate cyclase, Ca2+-activated K+ channels and hyperpolarization inhibition. Moreover, hinokitiol exhibited a blocking activity on Ca2+ mobilization through voltage dependent Ca2+ channels (VDCC). However, its effect was not changed by muscarinic receptor and Sarc-K+ ATP channels blocking but was enhanced by blocking voltage-dependent K+ channels. However, in angiotensin II-induced hypertension, hinokitiol vasodilating activity was attenuated by NOS inhibition and it blocked Ca2+ mobilization through VDCC, while its vasodilation was partially attenuated by Sarc-K+ ATP channels blocking. However, the vasodilating effect of hinokitiol was not attenuated by either cyclooxygenase, β-receptor, Ca2+-activated K+ channels, or voltage-dependent potassium channels inhibition, but was enhanced by blocking hyperpolarization. Hinokitiol's vasodilating effect in normotensive and hypertensive vessels is mediated through both endothelium-dependent and endothelium-independent mechanisms.

FRESH 3D Bioprinted Collagen‐based Resistance Vessels and Multiscale Vascular Microfluidics

The pursuit of an ideal model system to study the pathophysiology of vascular disease has included the use of tissue engineered blood vessels (TEBV), vascularizing engineered volumetric tissue, silicone‐based “organ‐on‐a‐chip” platform, and tissue decellularization; yet we are still far from generating engineered vascular tissue that recapitulate native physiology. Despite advances such as 3D bioprinting that have led to new approaches for creating fluidic channels, it remains challenging to produce continuous networks with vessels ranging from large (&gt;6 mm) to small (&lt;1 mm) using native‐like extracellular matrix (ECM) that recapitulates the mechanical properties, geometric organization, and complexity of the cellular and extracellular microenvironment. An ideal engineering strategy would combine the controlled fluid flow achieved by organ‐on‐a‐chip platforms with the ECM structure, composition, and biomechanics of decellularized tissue. Here, using Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D bioprinting, we spatially define ECM composition and vascular geometry to create collagen‐based microfluidics and an engineered resistance artery scaffold to study how ECM composition, mechanical properties, and fluid flow contribute to vascular disease. A 3D vascular microfluidic CAD model was designed with a hierarchically branching network containing a single inlet and outlet of 1 mm that branched down to 250 µm channels embedded within a collagen scaffold. This model was FRESH printed with 24 mg/mL collagen‐I and yielded a high‐fidelity scaffold with patent internal vasculature. 3D imaging and gauging analysis of the CAD model compared to the collagen scaffold revealed an average positive deviation of 9.9 µm and an average negative deviation of 56.3 µm. To interface with and perfuse the soft collagen microfluidic scaffold we 3D printed a custom bioreactor chamber for long‐term culture capable of &gt;1‐week perfusion under physiological conditions. In addition to embedded vascular networks, FRESH bioprinting allows for direct fabrication of suspended vessels. We designed an ECM scaffold scaled to match a resistance vessel consisting of a collagen‐I frame and suspended vessel (inner diameter of 300 µm, outer diameter of 500 µm). The collagen frame provides overall scaffold stability and allows interfacing to the custom perfusion bioreactor. Using multimaterial FRESH printing, we varied the ECM composition by patterning fibronectin along the inner lumen and collagen‐I within the outer adventitial wall. Biomechanical evaluation using pressure and wire myography revealed a burst pressure &gt;140 mmHg and an average peak tension of 600 mg, comparable to mouse mesenteric resistance arteries. Together, this work highlights the exciting potential for ECM‐based microfluidic scaffolds and vascular tissue engineering that will set the foundation for future work to replicate a healthy and hypertensive vessel microenvironment. In addition to vascular biology, the collagen‐based microfluidics are amenable to other organ systems, and can be utilized to study cell proliferation, metastasis, and ECM remodeling in a 3D environment.

Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension.

Our study aimed to examine the endothelium (vascular)-protecting effects of chronic cannabidiol (CBD) administration (10 mg/kg once daily for 2 weeks) in aortas and small mesenteric (G3) arteries isolated from deoxycorticosterone-induced hypertensive (DOCA-salt) rats and spontaneously hypertensive rats (SHR). CBD reduced hypertrophy and improved the endothelium-dependent vasodilation in response to acetylcholine in the aortas and G3 of DOCA-salt rats and SHR. The enhancement of vasorelaxation was prevented by the inhibition of nitric oxide (NO) with L-NAME and/or the inhibition of cyclooxygenase (COX) with indomethacin in the aortas and G3 of DOCA-salt and SHR, respectively. The mechanism of the CBD-mediated improvement of endothelial function in hypertensive vessels depends on the vessel diameter and may be associated with its NO-, the intermediate-conductance calcium-activated potassium channel- or NO-, COX-, the intermediate and the small-conductance calcium-activated potassium channels-dependent effect in aortas and G3, respectively. CBD increased the vascular expression of the cannabinoid CB1 and CB2 receptors and aortic levels of endocannabinoids with vasorelaxant properties e.g., anandamide, 2-arachidonoylglycerol and palmitoyl ethanolamide in aortas of DOCA-salt and/or SHR. In conclusion, CBD treatment has vasoprotective effects in hypertensive rats, in a vessel-size- and hypertension-model-independent manner, at least partly via inducing local vascular changes in the endocannabinoid system.

The inflammation influence on pathological remodeling of pulmonary arteries in monocrotaline-induced pulmonary hypertension in rats

Abstract Aim To investigate the inflammation role on pathological remodeling of pulmonary arteries (PA) in monocrotaline-induced pulmonary hypertension (mPAH) in rats with joint assessment serum and tissue inflammatory biomarkers and the morphological arteries changes. Methods The mPAH was induced by a subcutaneous monocrotaline injection (60 mg/kg) in male rats and control group received a single saline solution. Baseline and every 2, 4, 6, 8 weeks after the serum concentrations of interleukin-6 (IL-6), interleukin-10 (IL-10) were measured by enzyme-linked immunosorbent assay; matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), collagen type 1 and 3, smooth muscle actin α (SMA-α) in lung tissue were investigated immunohistochemically and quantitative measurements of intima and media thickness were done by planimetry. The functional activity neutrophil changes measured by chemiluminescence and fluorescent methods. Results The IL-10 increased after 2 weeks of mPAH (5,9 vs 0,6 pg/ml, p&amp;lt;0,05) vs control and then it decreased to initial values by 8 weeks (0,06 vs 0,62 pg/ml, p&amp;gt;0,05). The increasing IL-6 (30,3 vs 0,01 pg/ml, p&amp;lt;0,05) and the maximum expression of IL-1β in the lung tissue (0,119 vs 0,099 index of expression (IE), p&amp;lt;0,05) we observed 4 weeks after mPAH. The SMA-α (29,4 vs 40,2 IE, p&amp;lt;0,05) and MMP-9 (1,6 vs 0,8 IE, p&amp;lt;0,05) expression level significantly raised 4 weeks later vs control and remained in a high level until 8 week. A significant increase of type 1 collagen expression was observed at all phases of the experiment, and high level type 3 collagen expression was observed from 4 to 8 weeks (7,0 vs 10,4 IE, p&amp;lt;0,05). The histological characteristics of remodeling these were a thickening of the media (30,6 vs 56,0 μm, p&amp;lt;0,05) and the subintimal layer (1,6 vs 10,9 μm, p&amp;lt;0,05) of the PA. 2 weeks after mPAH cell priming occurred which manifested by modification ROS generation systems, decrease NADPH oxidase activity, increase of myeloperoxidase secretion (MPO), enhance of unbound cytosolic calcium ions, mitochondrial potential reduction. From 4 to 8 weeks an increase NADPH oxidase activity and MPO secretion was revealed into the extracellular environment which leads to overproduction of hypochlorous acid. This functional activity reprogramming of circulating neutrophils indicate associated with time-development of mPAH. Conclusion The inflammation is the most important mediator of pathological remodeling processes in mPA. The monocrotaline launches a neutrophil reaction at an early stage of PAH with changes their functional activity which leads to immune cells recruitment into the lung tissue, producing inflammation and proliferation biomarkers. The hyperplasia of smooth muscle cells and reconstruction of the extracellular matrix are the result of this process and leads to increase intima and media thickness. The high MMP-9, SMA-α, IL-6 activity in 6–8 weeks reflects maintenance local inflammatory potential. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Basic and applied sciences - medicine, subprogram “Diagnostics and therapy of diseases” on the assignment “To establish the molecular-cellular mechanisms of the development of irreversible remodeling of pulmonary vessels in pulmonary arterial hypertension in an experiment in vivo.”

Cinaciguat Prevents Postnatal Closure of Ductus Arteriosus by Vasodilation and Anti-remodeling in Neonatal Rats.

Closure of the ductus arteriosus (DA) involves vasoconstriction and vascular remodeling. Cinaciguat, a soluble guanylyl cyclase (sGC) activator, was reported with vasodilatory and anti-remodeling effects on pulmonary hypertensive vessels. However, its effects on DA are not understood. Therefore, we investigated whether cinaciguat regulated DA patency and examined its underlying mechanisms. In vivo, we found that cinaciguat (10 mg/kg, i.p. at birth) prevented DA closure at 2 h after birth with luminal patency and attenuated intimal thickening. These anti-remodeling effects were associated with enhanced expression of cyclic guanosine monophosphate (cGMP) in DA. Ex vivo, cinaciguat dilated oxygen-induced DA constriction dose-dependently. Such vasodilatory effect was blunted by KT-5823, a PKG inhibitor. In DA smooth muscle cells (DASMCs), we further showed that cinaciguat inhibited angiotensin II (Ang II)-induced proliferation and migration of DASMCs. In addition, cinaciguat inhibited Ang II-induced mitochondrial reactive oxygen species (ROS) production. Finally, Ang II-activated MAPKs and Akt were also inhibited by cinaciguat. In conclusion, cinaciguat prevents postnatal DA closure by vasodilation and anti-remodeling through the cGMP/PKG pathway. The mechanisms underlying anti-remodeling effects include anti-proliferation and anti-migration, with attenuation of mitochondrial ROS production, MAPKs, and Akt signaling. Thus, this study implicates that sGC activation may be a promising novel strategy to regulate DA patency.

Morphological assessment of pulmonary vessels in pulmonary arterial hypertension associated with congenital heart disease

Pulmonary vascular remodeling is the key structural alteration in pulmonary arterial hypertension associated with congenital heart disease (CHD). Changes in the pulmonary vessels in CHD generally occur in the inner and middle coats. This review considers the pathology of these changes and highlights some issues of a stereological approach to the morphometry of pulmonary vasculature. It also touches upon the issues of the morphology of pulmonary vessels in post-capillary and segmental pulmonary hypertension.

Результаты офтальмологического мониторинга пациентов с гипертонической болезнью и ишемической болезнью сердца

Aim: to study ophthalmological clinical functional parameters in patients with hypertension and coronary heart disease (CHD) with coronary artery stenosis. Patients and Methods: 30 patients (58 eyes) with hypertension and CHD with coronary artery stenosis (group A) and 30 healthy controls (60 eyes, group B) were examined. Best-corrected visual acuity (BCVA), macular sensitivity (MS) assessed by MAIA microperimetry, central macular thickness (CMT), foveal avascular zone (FAZ) area, vessel density of superficial capillary plexus (SCP VD) and deep capillary plexus (DCP VD) and choriocapillaris measured by optical coherence tomography angiography (OCTA) were evaluated. Results: FAZ area was 0.42±0.03 mm2 in group A and 0.28±0.03 mm2 in group B (p&lt;0.05). SCP VD was 11.4±3.1% in group A and 25.4±2.5% in group B (p&lt;0.05). DCP VD was 22.3±1.1% in group A and 39.2±3.5% in group B (p&lt;0.05). Choriocapillaris VD was 51.2±1.1% in group A and 63.1±1.2% in group B (p&lt;0.05). Correlations between ocular parameters and ejection fraction (EF) were revealed (BCVA: r=0.61, p&lt;0.05; MS: r=0.68, p&lt;0.05; CMT: r=-0.72, p&lt;0.05; FAZ: r=-0.73, p&lt;0.05; SCP VD: r=0.82, p&lt;0.05; DCP VD: r=0.81, p&lt;0.05; choriocapillaris VD: r=0.76, p&lt;0.05). Conclusions: in patients with hypertension and CHD with coronary artery stenosis, significant (p&lt;0.05) reduction in BCVA, MS, SCP VD, DCP VD, and choriocapillaris VD and increase in CMT and FAZ area were detected compared to healthy individuals. Additionally, strong correlations between ocular parameters (FAZ, SCP VD, DCP VD, and choriocapillaris VD) and EF (p&lt;0.05) were identified. OCTA may be recommended to monitor fundus vessels in hypertension and CHD as an effective noninvasive valuable diagnostic tool to verify hypertension and CHD. Keywords: hypertension, coronary heart disease, coronary artery stenosis, hypertensive retinopathy, foveal avascular zone, vessel density, optical coherence tomography angiography. For citation: Moshetova L.K., Vorobyeva I.V., Dgebuadze A. et al. Ophthalmological monitoring in patients with hypertension and coronary heart disease. Russian Journal of Clinical Ophthalmology. 2021;21(2):51–57. DOI: 10.32364/2311-7729-2021-21-2-51-57.

Regular Black Bean Consumption Is Necessary to Sustain Improvements in Small-Artery Vascular Compliance in the Spontaneously Hypertensive Rat.

Edible legume seeds, such as lentils, have been shown to modulate the structural and functional properties of hypertensive blood vessels, however, the effects of dried beans have not been similarly evaluated. To determine whether beans could attenuate hypertension-induced vascular changes (remodeling and stiffness) in relation to their phytochemical content, spontaneously hypertensive rats (SHR) were fed diets containing black beans (BB; high phytochemical content as indicated by their dark seed coat colour) or navy (white) beans (NB; low phytochemical content) for eight weeks. An additional follow-up phase was included to determine how long the alterations in vascular properties are maintained after bean consumption is halted. Assessments included blood pressure (BP), pulse wave velocity (PWV), vessel compliance (small-artery) and morphology (large-artery), and body composition. Neither BBs nor NBs altered BP or PWV in SHR. SHR-BB demonstrated greater medial strain (which is indicative of greater elasticity) at higher intraluminal pressures (80 and 140 mmHg) compared to SHR-NB. BB consumption for 8 weeks enhanced vascular compliance compared to SHR-NB, as demonstrated by a rightward shift in the stress–strain curve, but this improvement was lost within 2 weeks after halting bean consumption. BB and NB increased lean mass after 8 weeks, but halting BB consumption increased fat mass. In conclusion, regular consumption of BBs may be appropriate as a dietary anti-hypertensive strategy via their positive actions on vascular remodeling and compliance.

Abstract WP238: Atrial Fibrillation is Associated With Severe Basal Ganglia Perivascular Spaces

Introduction: High burdens of basal ganglia-perivascular spaces (BG-PVS) are often attributed to underlying hypertensive cerebral small vessel disease (HTN-CSVD). Although PVS are thought to arise from decreased perivascular drainage related to changes in arterial pulsatility, the contribution of pulsatility changes from nonvalvular atrial fibrillation (NVAF) has not been studied. Hypothesis: We hypothesized that NVAF patients have a higher burden of BG-PVS than HTN-CSVD patients, possibly through hemodynamic factors related to NVAF. Methods: Through an observational single-center study of consecutive stroke patients, we compared BG-EPVS severity between 136 patients with NVAF-related ischemic stroke (NVAF-IS) and 107 patients with HTN-CSVD-related intracerebral hemorrhage (HTN-ICH) without NVAF. Within the NVAF cohort, we also built multiple regression models to evaluate independent effects of NVAF-related factors on BG-PVS. All multiple regression models were adjusted for age, hypertension, sex, and neuroimaging markers of CSVD (extent of white matter hyperintensities (WMH), presence of lacunes, and cerebral microbleeds). Results: Patients with NVAF-IS were older than patients with HTN-ICH (75 + 12 vs. 64 + 13, p &lt; 0.0001); however, there was no difference in sex between groups ( p = 0.6). Severe BG-PVS (defined as &gt; 20 PVS in the BG) were found in 42.6% of NVAF-IS patients vs. 8.4% of HTN-ICH ( p &lt; 0.0001). Even after multivariate adjustment, the presence of NVAF remained significantly related to BG-PVS ( p = 0.001). Within the NVAF cohort, CHA2DS2-VASc was associated with the presence of severe BG-PVS ( p = 0.003) despite controlling for other covariates. When CHA2DS2-VASc was replaced with its individual components in the same regression model, congestive heart failure (CHF, p = 0.017), WMH burden ( p = 0.009), and age ( p = 0.02) were found to be predictors of severe BG-PVS. Conclusions: Severe BG-PVS were significantly more common in NVAF patients compared to HTN-CSVD patients. NVAF-related features (CHA2DS2-VASc score) and CHF were associated with higher burdens of BG-PVS. These findings suggest that NVAF might play a role in the development of BG-PVS, conceivably through hemodynamic factors.

Lycium barbarum polysaccharides related RAGE and Aβ levels in the retina of mice with acute ocular hypertension and promote maintenance of blood retinal barrier.

Our previous study verified the protective effects of Lycium barbarum polysaccharides (LBP) on retinal neurons and blood vessels in acute ocular hypertension (AOH) mice. To investigate the effect of LBP on the reactivity of retinal glial cells, an AOH mouse model was established in one eye by maintaining ocular hypertension of 90 mmHg for 60 minutes. Either LBP solution (1 mg/kg) or phosphate-buffered saline was administrated to the mice by gavage daily, starting 7 days before the AOH insult and continuing until the mice were sacrificed for specimen collection on day 4 post-insult. After AOH insult, increased numbers of astrocytes and microglia were observed, together with decreased expression of the following glial cell biomarkers in the retinal ganglion cells of AOH mice: glial fibrillary acidic protein, glutamine synthetase, aquaporin-4, S-100 proteins, ionized calcium-binding adaptor molecule 1, amyloid precursor protein and receptor of advanced glycosylation end-products. After intervention with LBP, the above changes were significantly reduced. Remarkably, morphological remodeling of blood vessel-associated retinal astrocytes, marked by glial fibrillary acidic protein, was also observed. These results, taken together, suggest that LBP regulated the production of amyloid-β and expression of receptor of advanced glycosylation end-products, as well as mediating the activity of retinal glial cells, which may lead to the promotion of better maintenance of the blood-retinal barrier and improved neuronal survival in AOH insult. This study was approved by the Committee for the Use of Live Animals in Teaching and Research (approval No. CULTRA-#1664-08).

Triiodothyronine Reduces Vascular Dysfunction Associated with Hypertension by Attenuating Protein Kinase G/Vasodilator-Stimulated Phosphoprotein Signaling.

Vascular dysfunction associated with hypertension comprises hypercontractility and impaired vasodilation. We have previously demonstrated that triiodothyronine (T3), the active form of thyroid hormone, has vasodilatory effects acting through rapid onset mechanisms. In the present study, we examined whether T3 mitigates vascular dysfunction associated with hypertension. To test the direct effects of T3 in hypertensive vessels, aortas from female Dahl salt-sensitive (Dahl SS) rats fed a high-salt diet (8% NaCl, HS group) and their age-matched controls fed a standard low-salt diet (0.3% NaCl, LS group) for 16 weeks were isolated and used in ex vivo vascular reactivity studies. We confirmed that the HS group exhibited a higher systolic blood pressure in comparison with the control LS group and displayed aortic remodeling. Aortas from both groups were pretreated with T3 (0.1 μM) for 30 minutes at 37°C in a 5% CO2 incubator before functional vascular studies. T3 treatment significantly attenuated hypercontractility and improved impaired endothelium-dependent vasodilation in aortas from the HS group. These vascular improvements in response to T3 were accompanied by increased phosphorylation of vasodilator-stimulated phosphoprotein (VASP) at serine 239, a vasodilatory factor of the cGMP-dependent protein kinase (PKG)/VASP signaling pathway in vascular smooth muscle cells. Moreover, increased production of reactive oxygen species in aortas from the HS group were significantly reduced by T3, suggesting a potential antioxidant effect of T3 in the vasculature. These results demonstrate that T3 can mitigate hypertension-related vascular dysfunction through the VASP signaling pathway and by reducing vascular ROS production. SIGNIFICANCE STATEMENT: This study demonstrates that triiodothyronine (T3) directly acts on vascular tone and has a beneficial effect in hypertension-induced vascular dysfunction. T3 augmented vasodilation and diminished vasoconstriction in blood vessels from hypertensive rats in association with activation of the protein kinase G/vasodilator-stimulated phosphoprotein signaling pathway that activates vascular relaxation and exerted an antioxidant effect. Collectively, these results show that T3 is a potential vasoprotective agent with rapid action on hypertension-related vascular dysfunction.

Decreased vasodilatory effect of Tanshinone ⅡA Sodium Sulfonate on mesenteric artery in hypertension

Tanshinone ⅡA Sodium Sulfonate (DS-201), a derivative of traditional Chinese medicinal herb Danshen, has been clinically used for various cardiovascular diseases. Previous studies showed that DS-201 induced vascular relaxation partly due to the activation of the large conductance Ca2+-activated potassium (BKCa) channels. However, the efficacy of DS-201 on the resistant vessels in hypertension remains unknown. Mesentery arteries obtained from spontaneously hypertensive rats (SHR) and hypertension patients were used in this study. The endothelium-denuded mesenteric arteries were prepared to measure the artery tension and evaluate the vasodilatory effect of DS-201. The results showed that DS-201 had a vasodilatory effect on the mesenteric artery rings pre-contracted with either phenylephrine (PE) or thromboxane mimetic U46619 in a concentration-dependent manner. However, the vasodilatory effect of DS-201 significantly decreased in hypertension than in control arteries due to a decrease in protein level of BKCa β1subunit. A BKCa channel blocker IbTX (200 nM) significantly inhibited the relaxant effect of DS-201 on non-hypertensive arteries, whereas the BKCa channel specific agonist NS1619 rescued the vasodilating effects of DS-201 on hypertensive vessels. These results indicate that the vasodilating effect of DS-201 is BKCa-dependent. This study demonstrated that DS-201 alone may not be effective for treating hypertension, but it may be considered as therapy combined with BKCa-agonists or methods rescuing BKCa functions.