Artery Rings Research Articles

Vieussens’ arterial ring to main pulmonary artery fistula in patient with chest pain

We report a rare case of Vieussens’ arterial ring to main pulmonary artery fistula in patient with chest pain who underwent computed tomography (CT) coronary angiography. This case highlights a rare type of coronary-pulmonary artery fistula and role of CT angiography in detecting such anomalies which carry important hemodynamic implications. It is imperative to treat such complicated cardiovascular anomalies to avoid possible long-term clinical consequences.

Abstract 4138424: Ring of Power: Unraveling a Rare Diagnosis in a Young Male with Palpitations

Case Description: A 36-year-old male presented for an outpatient treadmill ECG stress test for further evaluation of palpitations exacerbated by exercise. He had no ischemic ECG changes, but developed a sustained episode of polymorphic VT at 13 minutes (Figure 1a). The test was stopped and the VT self-terminated after 43 seconds. The patient was admitted for further workup. Lab workup was unremarkable; baseline ECG demonstrated no ST-T wave changes and displayed normal QT and QRS duration. TTE showed mild biventricular dysfunction. Coronary CT angiogram showed type 3 subtype of Vieussens’ arterial ring (VAR), with an absent left main and super-dominant RCA supplying both LAD and LCx. FFR-CT showed non-hemodynamically significant stenosis in the mid-distal LAD (Figure 1b). Left heart catheterization confirmed presence of VAR and mild diffuse disease in a small-caliber mid-distal LAD (Figures 1c&d). No malignant course or dynamic coronary compression was present. Cardiac MRI revealed normal biventricular function and the absence of late gadolinium enhancement. An exercise stress test, now with myocardial perfusion, was performed and was entirely normal without evidence of myocardial ischemia. Genetic testing for catecholaminergic polymorphic VT was negative. After a multidisciplinary discussion, it was decided not to pursue CABG in the absence of demonstrable ischemia at peak exercise. He underwent an ICD placement for secondary prevention and was discharged on beta blockers. Discussion: Three distinct subtypes of VAR have been described, with type 3 being the rarest. The coronary anomaly was first described by Raymond de Vieussens in 1706, and represents an embryologic remnant of the conotruncal circle. It may be diagnosed incidentally in asymptomatic patients or present with angina especially if underlying CAD, aneurysms or fistulae are present. We report the first case of exercise-induced polymorphic VT in a type 3 VAR patient, theorizing that intermittent myocardial ischemia at peak exercise may induce VT in these patients. Surgical revascularization may be considered if myocardial ischemia is demonstrated on stress testing, although its benefit in patients without such evidence of ischemia is unknown.

Abstract 4125587: Vasomotor function and its regulation by perivascular adipose tissue in metabolic syndrome vary depending on severity and combination of metabolic parameters

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease. Because perivascular adipose tissue (PVAT) regulates arterial tone by releasing vasorelaxing/vasocontracting factors, the effects of PVAT on vasomotor function have been heterogeneously reported. Various PVAT functions can result from the severity or combination of metabolic parameters in MetS. Therefore, we compared the effects of mesenteric arterial PVAT on the nitric oxide-dependent vasorelaxation response among the three metabolic syndrome (MetS) model strains. We compared male OLETF, Zucker fatty (ZF), and SHRSPZF (SPZF) rats aged 20 weeks to lean controls, LETO, ZF +/+ , and Wistar-Kyoto (WKY) rats. To determine the effects of PVAT on vasodilators, we used organ bath techniques to assay nitroprusside-induced relaxation of isolated mesenteric arterial ring preparations with intact or removed PVAT. The waist circumference to length ratio in OLETF and ZF rats was higher than that in SPZF rats, and the systolic blood pressure was higher in SPZF rats than in the other groups. In the serum, there was no significant difference in triglyceride levels. Still, glucose and thiobarbituric acid reactive substance levels were higher in OLETF and SPZF rats than in ZF rats. Relaxation in ZF rats did not change compared to that in ZF +/+ rats and the presence of PVAT. In contrast, relaxation in OLETF rats was lower than in LETO rats, and there was no difference between the presence and absence of PVAT. However, relaxation in SPZF rats was lower than in WKY rats, and relaxation increased to the same level as in WKY rats in the presence of PVAT. This study unveils novel insights, suggesting that high serum glucose and oxidative stress cause arterial dysfunction, whereas high blood pressure induces PVAT functional changes. These findings underscore the complex interplay between metabolic disorders and vascular health, potentially paving the way for more targeted interventions in patients with MetS.

Abstract 4135035: Liver kinase B1 (LKB1) loss links vascular smooth muscle cell fate switch to aortic aneurysm formation

Background: Acquisition and maintenance of vascular smooth muscle cell (VSMC) fate are important for vascular development and homeostasis; however, little is known about the key determinant for VSMC fate and vascular homeostasis. Methods: Lkb1 flox/flox ; Tagln- Cre, Lkb1 flox /flox ; Myh11-Cre/ERT2 , and lineage tracing Lkb1 flox/flox ; Myh11-Cre/ERT2 ; ROSA mT/mG mice were generated to study the impact of Lkb1 on VSMC and vascular function in vivo . Single aortic cells isolated from wild-type and Lkb1 flox/flox ; Myh11-Cre/ERT2 mice were analyzed by single-cell RNA sequencing (sc-RNA seq). The dynamic changes of vascular morphology and VSMC fate were investigated using high-frequency ultrasound and various histological techniques. In addition, VSMC phenotype and molecular mechanisms were further explored by mouse arterial ring assay ex vivo , in cultured human aortic VSMC in vitro, and in human aneurysmal aortic tissues. Results: We found that SMC-specific Lkb1 ablation in Lkb1 flox/flox ; Tagln-Cre mice caused severe vascular abnormalities and embryonic lethality. SMC-specific deletion of Lkb1 in tamoxifen-inducible Lkb1 flox/flox ; Myh11-Cre/ERT2 mice spontaneously and progressively induced aortic/arterial dilation, aneurysm, rupture, and premature death. Sc-RNA seq and imaging-based lineage tracing showed that Lkb1 -deficient VSMCs transdifferentiated gradually from early modulated VSMCs to fibroblast-like and chondrocyte-like cells, leading to ossification and blood-vessel rupture. Moreover, we found that SMC-specific Lkb1 ablation resulted in decreased vascular contractility and hypotension in vivo . Mechanistically, Lkb1 regulates polypyrimidine tract binding protein 1 (Ptbp1) expression and controls alternative splicing of pyruvate kinase muscle (PKM) isoforms 1 and 2. Lkb1 loss in VSMC results in an increased PKM2/PKM1 ratio and alters the metabolic profile by promoting aerobic glycolysis. Treatment with PKM2 activator TEPP-46 rescues VSMC transformation and aortic dilation in Lkb1 flox/flox ; Myh11-Cre/ERT2 mice. Furthermore, we found that Lkb1 expression decreased in human aortic aneurysm tissue compared to control tissue, along with changes in markers of VSMC fate. Conclusions: Lkb1, via its regulation of Ptbp1-dependent alterative splicing of PKM, maintains VSMC in contractile states and sustains vascular homeostasis. Our findings have important implications for understanding the pathogenesis of aortic aneurysm.

Unveiling Vieussens' Arterial Ring: A Case Report of an Uncommon Coronary Anomaly with Obstructive Coronary Artery Disease

Unveiling Vieussens' Arterial Ring: A Case Report of an Uncommon Coronary Anomaly with Obstructive Coronary Artery Disease

4-Octyl itaconate inhibits vascular calcification partially via modulation of HMOX-1 signaling

Vascular calcification frequently occurs in patients with chronic conditions such as chronic kidney disease (CKD), diabetes, and hypertension and represents a significant cause of cardiovascular events. Thus, identifying effective therapeutic targets to inhibit the progression of vascular calcification is essential. 4-Octyl itaconate (4-OI), a derivative of itaconate, exhibits anti-inflammatory and antioxidant activity, both of which play an essential role in the progression of vascular calcification. However, the role and molecular mechanisms of 4-OI in vascular calcification have not yet been elucidated. In this study, we investigated the effects of exogenous 4-OI on vascular calcification using vascular smooth muscle cells (VSMCs), arterial rings, and mice. Alizarin red staining and western blot revealed that 4-OI inhibited calcification and osteogenic differentiation of human VSMCs. Similarly, 4-OI inhibited calcification of rat arterial rings and VitD3-overloaded mouse aortas. Mechanistically, RNA sequencing analysis revealed that 4-OI treatment is most likely to affect heme oxygenase 1 (HMOX-1) mRNA expression. The study demonstrated that 4-OI treatment increased HMOX-1 mRNA and protein levels, but suppressed inflammation and oxidative stress in VSMCs under osteogenic conditions. Moreover, 4-OI treatment. HMOX-1 knockdown by siRNA or treatment with the HMOX-1 inhibitor ZnPP9 significantly reversed the suppression effect on calcification of VSMCs and aortas of VitD3-overloaded mice by 4-OI. Furthermore, HMOX-1 knockdown by siRNA markedly abrogated the inhibitory effect of 4-OI on inflammation in VSMCs. These findings suggest that 4-OI alleviates vascular calcification and inhibits oxidative stress and inflammation through modulation of HMOX-1, indicating its potential as a therapeutic target for vascular calcification.

Danggui Buxue Decoction and its components dilate coronary artery through activating the inward rectification K+ channels pathway

Ethnopharmacological relevanceDanggui Buxue Decoction (DBD), a classic representative prescription of invigorating Qi and producing blood, is used to treat coronary heart disease angina pectoris and vascular injury diseases. Abnormal coronary artery is an important cause of cardiovascular disease. However, the mechanism of DBD dilates coronary arteries is still unclear. Aim of the studyThis study aimed to elucidate the impacts and distinctions among DBD, Astragalus, Angelica sinensis, and identified active components on pre-constricted coronary arteries, as well as to delve deeper into their respective mechanisms. Materials and methodsAfter the preconstriction of a rat isolated coronary artery ring with either 30 mM KCl or 200 nM U46619, the vascular tension was observed following the addition of DBD, and other components. Subsequently, the impact of these active components on coronary blood flow (CBF) was confirmed through in vivo testing. Further investigation into the underlying mechanism was carried out using a combination of blockers, molecular docking, surface plasmon resonance (SPR), cell heat transfer analysis (CETSA), and patch-clamp techniques. ResultsIn vitro experiments showed that DBD and its components butylidenephthalide, ligustilide, calycosin, and quercetin could dilate coronary artery preconstricted with either 30 mM KCl or 200 nM U46619. In addition, the active ingredient was found to significantly increase CBF. Mechanistically, BaCl2 was found to reduce the relaxation effect of the drug by adding a blocker. Molecular docking, SPR and CETSA results showed that the active ingredients had a strong binding potential with inward rectification K+ channels (KIR) channel protein. Patch clamp studies demonstrate that quercetin can increase KIR current, and BaCl2 can significantly reduce its current. ConclusionsThe active components of DBD, butylidenephthalide, ligustilide, calycosin, and quercetin, activate KIR channels to relax coronary artery and increase CBF.

Right coronary ostial atresia with Vieussens’ arterial ring

Right coronary ostial atresia with Vieussens’ arterial ring

A Skeletal Muscle-Mediated Anticontractile Response on Vascular Tone: Unraveling the Lactate-AMPK-NOS1 Pathway in Femoral Arteries.

The regulation of vascular tone by perivascular tissues is a complex interplay of various paracrine factors. Here, we investigate the anti-contractile effect of skeletal muscle surrounding the femoral and carotid arteries and its underlying mechanisms. Using male and female Wistar rats, we demonstrated that serotonin, phenylephrine, and U-46619 induced a concentration-dependent vasoconstrictor response in femoral artery rings. Interestingly, this response was diminished in the presence of surrounding femoral skeletal muscle, irrespective of sex. No anti-contractile effect was observed when the carotid artery was exposed to its surrounding skeletal muscle. The observed effect in the femoral artery persisted even in the absence of endothelium and when the muscle was detached from the artery. Furthermore, the skeletal muscle surrounding the femoral artery was able to promote an anti-contractile effect in three other vascular beds (basilar, mesenteric, and carotid arteries). Using inhibitors of lactate dehydrogenase and the 1/4 monocarboxylate transporter, we confirmed the involvement of lactate, as both inhibitors were able to abolish the anti-contractile effect. However, lactate did not directly promote vasodilation; rather, it exerted its effect by activating 5' AMP-activated protein kinase (AMPK) and neuronal nitric oxide synthase (NOS1) in the skeletal muscle. Accordingly, Nω-propyl L-arginine, a specific inhibitor of NOS1, prevented the anti-contractile effect, as well as lactate-induced phosphorylation of NOS1 at the stimulatory serine site (1417) in primary skeletal muscle cells. Phosphorylation of NOS1 was reduced in the presence of Bay-3827, a selective AMPK inhibitor. In conclusion, femoral artery-associated skeletal muscle is a potent paracrine and endocrine organ that influences vascular tone in both sexes. Mechanistically, the anti-contractile effect involves muscle fiber type and/or its anatomical location but not the type of artery or its related vascular endothelium. Finally, the femoral artery anti-contractile effect is mediated by the lactate-AMPK-phospho-NOS1Ser1417-NO signaling axis.

Quadricuspid aortic valve and its rare association with left main obstruction: case report and literature review.

The quadricuspid aortic valve (QAV) is a rare congenital anomaly. We report a 51-year-old woman with QAV who experienced intermittent chest pain due to fibrotic tissue overgrowth from the small left coronary cusp, obstructing the left main coronary artery (LM). Angiography revealed a large "Vieussens' arterial ring," which acted as a collateral channel from the right coronary artery to the left coronary artery, preserving coronary blood flow and left ventricular function. Surgery successfully removed the tissue, maintaining both aortic valve function and coronary patency. This case highlights the need to consider QAV complications and use various imaging modalities for accurate diagnosis and treatment planning, including evaluating potential issues like aortic regurgitation and coronary anomalies.

Abstract P139: Exploring the cardiometabolic effects of lipid 12-hydroxyeicosapentaenoic acid through thromboxane receptor partial agonism

Introduction: It is well known that lipid mediators secreted by brown adipose tissue (BAT) during cold exposure or beta-adrenergic stimulation can exert beneficial effects on glucose and lipoprotein homeostasis. Recently, Leiria et al. demonstrated that one of these mediators, 12-hydroxyeicosapentaenoic acid (12-HEPE), secreted by BAT, enhances glucose tolerance and insulin sensitivity through the stimulation of a G protein-coupled receptor (GPCR). However, the receptor that 12(S)-HEPE binds to exert its functions was unknown. Therefore, this study aimed to identify the GPCR that 12-HEPE binds to and to investigate whether 12-HEPE affects vascular reactivity. Methods: Screening of 70 non-olfactory GPCR candidates was conducted in HEK293 cells, either stimulated or not with 12-HEPE (5µM). Receptor activation was measured using the dynamic mass redistribution (DRM) assay. After identifying the potential receptor, we validated the result by monitoring intracellular Ca2+ levels through a dose-response curve for 12-HEPE. To study the biological effects resulting from this ligand-receptor interaction, thoracic aortic artery rings were isolated from 12-week-old C57BL6 male mice, and their contractile responses were monitored using a myograph in response to cumulative doses ranging from 100pM to 10µM of 12-HEPE. Results: Through DRM screening, we found that the thromboxane receptor (TP) exhibited the strongest interaction with 12(S)-HEPE (5µM). To validate the screening, we incubated HEK293 cells with 12-HEPE or U46619 and quantified intracellular calcium mobilization. Our data demonstrate that 12-HEPE is a partial TP agonist, with an EC50 of 314nM compared to 7.2nM for U46619. Furthermore, incubation of the thoracic aorta with 12-HEPE produced dose-dependent increases in arterial constriction (pEC50: 6.129 ± 0.174; Emax: 95.39 ± 15.72), and this effect was completely prevented by the thromboxane antagonist, TPA (1µM). Conclusions: Our results suggest that 12-HEPE is an endogenous partial agonist of the TP receptor, and such interaction is necessary for the biological effects of these lipids. Importantly, the vasoconstrictor effect mediated by 12-HEPE may be an important physiological adaptation to prevent body heat loss upon cold exposure, thus allowing for adequate temperature maintenance.

Phoenixin-14 maintains the contractile type of vascular smooth muscle cells in cerebral aneurysms rats.

The rupture of intracranial aneurysm (IA) is the primary reason contributing to the occurrence of life-threatening subarachnoid hemorrhages. The oxidative stress-induced phenotypic transformation from the contractile phenotype to the synthetic phenotype of vascular smooth muscle cells (VSMCs) plays a pivotal role in IA formation and rupture. Our study aimed to figure out the role of phoenixin-14 in VSMC phenotypic switching during the pathogenesis of IA by using both cellular and animal models. Primary rat VSMCs were isolated from the Willis circle of male Sprague-Dawley rats. VSMCs were stimulated by hydrogen peroxide (H2O2) to establish a cell oxidative damage model. After pretreatment with phoenixin-14 and exposure to H2O2, VSMC viability, migration, and invasion were examined through cell counting kit-8 (CCK-8), wound healing, and Transwell assays. Intracellular reactive oxygen species (ROS) production in VSMCs was evaluated by using 2',7'-Dichlorofluorescin diacetate (DCFH-DA) fluorescence probes and flow cytometry. Rat IA models were established by ligation of the left common carotid arteries and posterior branches of both renal arteries. The histopathological changes of rat intracranial blood vessels were observed through hematoxylin and eosin staining. The levels of contractile phenotype markers (alpha-smooth muscle actin [α-SMA] and smooth muscle 22 alpha [SM22α]) in VSMCs and rat arterial rings were determined through real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Our results showed that H2O2 stimulated the production of intracellular ROS and induced oxidative stress in VSMCs, while phoenixin-14 pretreatment attenuated intracellular ROS levels in H2O2-exposed VSMCs. H2O2 exposure promoted VSMC migration and invasion, which, however, was reversed by phoenixin-14 pretreatment. Besides, phoenixin-14 administration inhibited IA formation and rupture in rat models. The decrease in α-SMA and SM22α levels in H2O2-exposed VSMCs and IA rat models was antagonized by phoenixin-14. Collectively, phoenixin-14 ameliorates the progression of IA through preventing the loss of the contractile phenotype of VSMCs.

Citrulline activates adenosine receptors: New insight into metabolic pathways interaction

Citrulline is a non-proteinogenic amino acid that forms as by-product in nitric oxide (NO) synthesis from arginine and may act in concert with NO as an independent signaling molecule that involves in the mechanism of vascular smooth muscle vasodilation.In this study we examined the effects of citrulline on pulmonary artery smooth muscles. Experimental design comprised outward potassium currents measurements in enzymatically isolated rat pulmonary artery smooth muscle (PASMc) cells using whole-cell patch clamp technique, isometric contractile force recordings on rat pulmonary artery rings and method of molecular docking simulation.Citrulline in a concentration 10−9-10−5 M relaxed phenylephrine (PHE)-preactivated SM of rat pulmonary artery in a dose-dependent manner (EC50 0,67 μM). This citrulline-induced relaxation was dependent on an intact endothelium. Bath application of citrulline (10-8-10-5 M) on isolated PASMc induced a significant increase in the amplitude of outward potassium current (Ik). The adenosine antagonist caffeine (10-6 M) effectively blocked both the citrulline-induced relaxation response and Ik increment. Molecular docking modeling suggests that caffeine blocking the potent activity of citrulline results from competitive interactions at the A2 adenosine receptor binding site.In summary, our data suggest that citrulline, released with NO at low concentrations, can effectively interact with adenosine receptors in smooth muscle cells, causing their relaxation, indicating surprising interaction between NO and adenosine pathways.

Role of Phenylethanolamine-N-methyltransferase on Nicotine-Induced Vasodilation in Rat Cerebral Arteries.

The sympathetic-parasympathetic (or axo-axonal) interaction mechanism mediated that neurogenic relaxation, which was dependent on norepinephrine (NE) releases from sympathetic nerve terminal and acts on β2-adrenoceptor of parasympathetic nerve terminal, has been reported. As NE is a weak β2-adrenoceptor agonist, there is a possibility that synaptic NE is converted to epinephrine by phenylethanolamine-N-methyltransferase (PNMT) and then acts on the β2-adrenoceptors to induce neurogenic vasodilation. Blood vessel myography technique was used to measure relaxation and contraction responses of isolated basilar arterial rings of rats. Nicotine-induced relaxation was sensitive to propranolol, guanethidine (an adrenergic neuronal blocker), and Nω-nitro-l-arginine. Nicotine- and exogenous NE-induced vasorelaxation was partially inhibited by LY-78335 (a PNMT inhibitor), and transmural nerve stimulation depolarized the nitrergic nerve terminal directly and was not inhibited by LY-78335; it then induced the release of nitric oxide (NO). Epinephrine-induced vasorelaxation was not affected by LY-78335. However, these vasorelaxations were completely inhibited by atenolol (a β1-adrenoceptor antagonist) combined with ICI-118,551 (a β2-adrenoceptor antagonist). These results suggest that NE may be methylated by PNMT to form epinephrine and cause the release of NO and vasodilation. These results provide further evidence supporting the physiological significance of the axo-axonal interaction mechanism in regulating brainstem vascular tone.

Abstract 1107: Unveiling Sex-based Differences In Plaque Histology In Patients With End-stage Peripheral Arterial Disease

Introduction: Recent studies on peripheral arterial disease (PAD) indicate prevalence of PAD in women to be equally if not greater than men, also suggesting that the latter have poorer outcomes with endovascular treatments. Hypothesis: Sex-related differences in treatment outcomes in PAD may be attributed to variations within the vessel wall. Aims: To evaluate sex-based differences in calcification patterns and lesion characteristics in PAD patients. Methods: 35 legs from 34 PAD patients (15 women) undergoing major amputation were collected. Vessels were harvested and cross-sectioned at 3-4 mm intervals, followed by histochemical staining, resulting in 1,278 arterial rings, each analyzed by an expert cardiovascular histopathologist. Results: Calcification was more prevalent in men (78.1%) than women (67.2%), though not significantly (p=0.118). The majority of calcified segments were concentric (>75% of circumference) for both men and women (66.7% and 64.4%, respectively). Women had a greater occurrence of predominantly medial calcification than men (73.3% vs. 65.3%, p=0.145). Of atherosclerotic features, men presented more fibrocalcific lesions (46.9% vs. 31.3%, p=0.023), while fibroatheroma (7.5%, vs men 4.2%, p=0.280) and fibrous plaque (10.4%, vs men 4.2% p=0.072) were more prevalent in women). In non-atherosclerotic segments, adaptive intimal thickening was more prevalent in men (37.5%) than women (16.4%, p<.001). Luminal thrombus was typically seen in women (38.7% vs. 25.0%, p=0.016), mostly presenting in an organized, chronic form in women (26.9% vs. men: 10.4%, p=0.016) and an acute form in men (6.3% vs. women: 0.0%, p=0.016). Conclusions: The localization of calcium, differences between atherosclerotic and non-atherosclerotic features, as well as the presence and form of luminal thrombus may guide treatment choices. Further studies are warranted to evaluate the impact of these differences on outcomes of endovascular procedures.

BLOOD PRESSURE, RENAL ARTERIAL FUNCTION AND OXIDATIVE-NITRATIVE STRESS IN A RAT MODEL OF POLYCYSTIC OVARY SYNDROME

Objective: Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder in women, is associated with elevated cardiovascular risk and vitamin D deficiency. This study evaluates blood pressure, renal arterial function and oxidative stress in a rat PCOS model, also exploring the impact of vitamin D supplementation. Assessing mean arterial blood pressure under anesthesia, renal arterial function and oxidative stress in a hyperandrogenic rat model, and the effectiveness of vitamin D substitution. Design and method: Thirty-two adolescent female Wistar rats were randomly assigned into four groups. Eight rats received no treatment (controls, C), eight received weekly Vitamin D per os (140 IU/100 g body weight, group D), eight received cutaneous testosterone daily (3.3 mg/100 g, T), and eight received Vitamin D and testosterone together (T+D). In the eighth week of the treatment, rats were anaesthetized with urethane, and blood pressure (MABP) was measured. The isolated renal arterial rings were cut into 3-4 mm long segments for wire myography. Other segments were formaldehyde-fixed and paraffin-embedded for histological evaluations. By immunohistochemical methods, we assessed the oxidative stress marker 4-hydroxynoneal (HNE) and poly(ADP-ribose) polymerase activation shown by nuclear poly(ADP-ribose) polymer (PAR). Results: MABP was lower in hyperandrogenic rats, which was not altered by Vitamin D supplementation. Phenylephrine-induced contraction (Phe) in 10-9-10-7 M concentrations was identical in all groups; however, 10-6 M Phe caused a lower contraction in D and T rats (54.4± 21% and 41.9±20% vs. C: 72.78±8% and T+D: 69.68±21%. p<0.05) compared to controls and double treated animals. Endothelium-mediated relaxation did not differ between groups. PAR staining was also identical, but HNE staining showed a tendency for increment in group T (p=0.12) but not in T+D. Conclusions: The decreased mean arterial pressure is likely the result of the compromised sensitivity to alpha1-adrenergic stimulus. The reduced reactivity of the renal artery may influence the activity of the renin-angiotensin-aldosterone system (RAAS). By normalizing the phenylephrine-induced contraction, Vitamin D supplementation might restore RAAS, thus blood pressure regulation.

The Vasodilator Effect and Mechanism of 18β-glycyrrhetinic Acid on Isolated Pulmonary Artery Rings in Rats

Background: The purpose of this study was to evaluate the effect of 18β-glycyrrhetinic acid (18β-GA) on isolated rat pulmonary artery vascular rings as well as the mechanism that lies behind the diastolic effects of this compound. Methods: To examine the effects of various doses of 18β-GA on resting normal vascular rings, we used isolated rat pulmonary artery vascular rings. The isolated rat pulmonary artery vascular ring was precontracted with phenylephrine (PE) and potassium chloride solution (KCl), which allowed for the observation of the diastolic effects of 18β-GA, as well as the effects of various concentrations of 18β-GA on blocking the four potassium channels of glibenclamide, barium chloride (BaCl2), tetraethylamine (TEA), or 4-aminopyridine; the impact of various 18β-GA concentrations on the pulmonary artery vasodilation effect pre-use of the nitric oxide synthase inhibitors l-nitroarginine methyl ester and indomethacin. Results: It was shown that 18β-GA has concentration-dependent diastolic effects on isolated rat pulmonary vascular rings that have been precontracted with PE and KCl but it has no effect on resting isolated thoracic aortic vascular rings. Conclusion: The two Kir and Kv channels may be connected to the endothelium-dependent vasodilation mechanism of 18β-GA.

Sulodexide Inhibits Arterial Contraction via the Endothelium-Dependent Nitric Oxide Pathway.

Background/Objectives: Sulodexide (SDX) is a drug known for restoring the glycocalyx, thereby offering endothelial protection and regulating permeability. Additionally, it has antithrombotic and anti-inflammatory properties and has shown arterial vasodilatory effects. Endothelial cells play a crucial role in maintaining homeostasis, with their dysfunction being a key contributor to loss in vasodilatory response, especially in arterial pathologies. The aim of this study was to investigate the effects of SDX on stimulated vascular tonus in human arterial samples and to assess the function of the endothelial layer as a source of nitric oxide (NO). Methods: A total of 16 internal mammary artery remnants from coronary artery bypass graft surgeries were dissected into endothelium-intact and endothelium-denuded groups (n = 8 each). The arterial rings were equilibrated under tension, with their basal tonus recorded before and after phenylephrine stimulation. SDX's impact on arterial contraction was assessed through cumulative dose-response curves. NO synthase inhibitor (Nω-nitro-L-arginine methyl ester) was used to assess SDX's vasodilatory effect over the NO pathway. Results: SDX application resulted in concentration-dependent vasorelaxation in both endothelium-intact and endothelium-denuded groups at certain doses. However, the inhibitory effect of SDX was more pronounced in endothelium-intact rings at higher doses compared to endothelium-denuded rings (p < 0.05). Similar inhibition of contraction curves was achieved for both endothelium-intact and endothelium-denuded rings after L-NAME pre-incubation, suggesting a necessity for NO-related endothelial pathways. Conclusions: SDX exerts a concentration-dependent inhibition on arterial contraction, emphasizing the critical role of an intact endothelium and NO-mediated pathways in this process. This underscores SDX's potential in treating endothelial dysfunction-related pathologies.

Oxidized phospholipid POVPC contributes to vascular calcification by triggering ferroptosis of vascular smooth muscle cells.

Vascular calcification is an actively regulated biological process resembling bone formation, and osteogenic differentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in this process. 1-Palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), an oxidized phospholipid, is found in atherosclerotic plaques and has been shown to induce oxidative stress. However, the effects of POVPC on osteogenic differentiation and calcification of VSMCs have yet to be studied. In the present study, we investigated the role of POVPC in vascular calcification using invitro and exvivo models. POVPC increased mineralization of VSMCs and arterial rings, as shown by alizarin red staining. In addition, POVPC treatment increased expression of osteogenic markers Runx2 and BMP2, indicating that POVPC promotes osteogenic transition of VSMCs. Moreover, POVPC increased oxidative stress and impaired mitochondria function of VSMCs, as shown by increased ROS levels, impairment of mitochondrial membrane potential, and decreased ATP levels. Notably, ferroptosis triggered by POVPC was confirmed by increased levels of intracellular ROS, lipid ROS, and MDA, which were decreased by ferrostatin-1, a ferroptosis inhibitor. Furthermore, ferrostatin-1 attenuated POVPC-induced calcification of VSMCs. Taken together, our study for the first time demonstrates that POVPC promotes vascular calcification via activation of VSMC ferroptosis. Reducing the levels of POVPC or inhibiting ferroptosis might provide a novel strategy to treat vascular calcification.

Resveratrol attenuates cyclosporin A-induced upregulation of the thromboxane A2 receptor and hypertension via the AMPK/SIRT1 and MAPK/NF-κB pathways in the rat mesenteric artery

Cyclosporin A, an immunosuppressive agent, is extensively utilized for the prevention of transplant rejection and treat autoimmune disease in the clinic, despite its association with a high risk of hypertension development among patients. Resveratrol is a kind of non-flavonoid phenolic compound that widely exists in many plants. The aim of the present study was to investigate the mechanism by which resveratrol ameliorates cyclosporin A-induced hypertension. The arterial rings of the mesentery were incubated with cyclosporin A and resveratrol in vitro. Rats were administered cyclosporin A and/or resveratrol for 3 weeks in vivo. Blood pressure was measured via the tail arteries. Vasoconstriction curves were recorded using a sensitive myograph. The protein expression was evaluated through Western blotting. This study demonstrated that resveratrol mitigated the cyclosporin A-induced increase in blood pressure in rats. Furthermore, resveratrol markedly inhibited the cyclosporin A-induced upregulation of thromboxane A2 receptor-mediated vasoconstriction in the rat mesenteric artery both in vitro and in vivo. Moreover, resveratrol activated AMPK/SIRT1 and inhibited the MAPK/NF-κB signaling pathway. In conclusion, resveratrol restored the cyclosporin A-induced upregulation of the thromboxane A2 receptor and hypertension via the AMPK/SIRT1 and MAPK/NF-κB pathways in rats.