Contraction Of Arteries Research Articles

Differential Suppressive Effects of Rho Kinase Inhibitor Fasudil on Serotonin- and Noradrenaline-Induced Contractions of Human Internal Thoracic Arteries and Saphenous Veins.

Rho kinase inhibitor fasudil exerts therapeutic effects against vasospasms. In this study, we aimed to compare its suppressive effects on serotonin (5-HT)- and noradrenaline (NAd)-induced contractions of human endothelium-denuded internal thoracic arteries (ITAs) and saphenous veins (SVs). NAd and 5-HT induced concentration-dependent contractions in both ITAs and SVs. However, fasudil (3 µmol/L) pretreatment decreased these constrictor-induced contractions in both ITAs and SVs. Fasudil exerted similar inhibitory effects on 5-HT and NAd in ITAs. However, in SVs, fasudil exerted stronger inhibitory effects on NAd-induced contractions than on 5-HT-induced contractions. Therefore, inhibitory effects of fasudil on 5-HT-induced contractions were stronger in ITAs than in SVs. Overall, these results suggest that Rho kinases exert different effects on the two vasoconstrictors in SVs, but not in ITAs, thus explaining their different graft patencies.

O65 SARCOPLASMIC CALCIUM ATPASE (SERCA) PROTEOLYSIS BY MATRIX METALLOPROTEINASE (MMP)-2 CONTRIBUTES TO VASCULAR DYSFUNCTION IN EARLY HYPERTENSION

Background and objective: Hypertension-induced increased matrix metalloproteinase (MMP)-2 activity proteolyzes extra- and intracellular proteins in aortas and contributes to vascular dysfunction. MMP-2 proteolyzes sarcoplasmic reticulum calcium ATPase (SERCA) in the heart during ischemia and reperfusion injury, thus impairing cardiac function. SERCA activity is also impaired in the arteries of hypertensive animals. We investigated whether hypertension-induced increased MMP-2 activity in aorta contributes to SERCA proteolysis, vascular remodeling and dysfunction. Methods: Aortas from male Sprague-Dawley (SD) rats, incubated or not with angiotensin II (AngII) and MMP inhibitors, ONO-4817 or doxycycline (Doxy), were used for zymography and co-immunoprecipitation of SERCA with MMP-2. Male SD rats were also submitted to two kidney-one clip (2K-1C) or Sham surgery and treated with Doxy from third to seventh day post-surgery. Systolic blood pressure (SBP) was assessed basally and daily by tail-cuff plethysmography. After 7 days, aortas were collected for gel and in situ zymography, western blot to SERCA, ATPase activity assay, vascular reactivity to phenylephrine and acetylcholine, Ki-67 immunofluorescence and hematoxylin/eosin stain. A7r5 cells were incubated or not with AngII, in the presence or absence of SERCA inhibitor, tapsigargin, to assess intracellular calcium concentrations. Results: AngII increased MMP-2 activity in aortas and MMP-2 co-immunoprecipitated with SERCA. SBP was increased in 2K-1C rats and Doxy did not reduce it, but decreased MMP-2 activity and prevented SERCA proteolysis in aortas. Intracellular calcium concentrations were increased in A7r5 cells incubated with AngII and/or SERCA inhibitor, tapsigargin. Cross sectional area, media to lumen ratio and Ki-67 were all increased in the aortas of hypertensive rats and Doxy decreased Ki-67 cell proliferation. In 2K-1C rats, arterial contraction to phenylephrine was accentuated but Doxy ameliorated only the impaired relaxation to acetylcholine. Conclusion: Doxy reduced MMP-2 activity in the aortas of 2K-1C rats and prevented the ATPase activity impairment and MMP-2-induced SERCA proteolysis and vascular dysfunction.

Vascular smooth muscle BK channels limit ouabain-induced vasocontraction: Dual role of the Na/K-ATPase as a hub for Src-kinase and the Na/Ca-exchanger.

Large-conductance, calcium-activated potassium channels (BK channels) and the Na/K-ATPase are expressed universally in vascular smooth muscle. The Na/K-ATPase may act via changes in the intracellular Ca2+ concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels. Whether BK channels functionally interact in vascular smooth muscle cells with the Na/K-ATPase remains to be elucidated. Thus, this study addressed the hypothesis that BK channels limit ouabain-induced vasocontraction. Rat mesenteric arteries were studied using isometric myography, FURA-2 fluorimetry and proximity ligation assay. The BK channel blocker iberiotoxin potentiated methoxamine-induced contractions. The cardiotonic steroid, ouabain (10-5 M), induced a contractile effect of IBTX at basal tension prior to methoxamine administration and enhanced the pro-contractile effect of IBTX on methoxamine-induced contractions. These facilitating effects of ouabain were prevented by the inhibition of either NCX or Src kinase. Furthermore, inhibition of NCX or Src kinase reduced the BK channel-mediated negative feedback regulation of arterial contraction. The effects of NCX and Src kinase inhibition were independent of each other. Co-localization of the Na/K-ATPase and the BK channel was evident. Our data suggest that BK channels limit ouabain-induced vasocontraction by a dual mechanism involving the NCX and Src kinase signaling. The data propose that the NCX and the Src kinase pathways, mediating the ouabain-induced activation of the BK channel, act in an independent manner.

Perinatal hypoxia augments contractile impact of NADPH oxidase-derived ROS in early postnatal rat arteries.

Reactive oxygen species (ROS), including those produced by NADPH oxidase (NOX), play an important vasomotor role, especially at early postnatal period. Mechanisms for regulating vascular tone can change significantly due to neonatal asphyxia and accompanying hypoxia. We tested the hypothesis that normobaric hypoxia (8% O2) for 2 h at the second day of life changes the functional contribution of NOX-derived ROS to the regulation of agonist-induced contraction in early postnatal rats. We studied saphenous arteries from 11- to 14-day-old male offspring using isometric myography and Western blotting and assessed the content of biochemical parameters in blood serum. The values of main biochemical parameters in blood serum and the protein content of NOXs and superoxide dismutases in arterial tissue did not differ between "Control" and "Hypoxia" pups. The NOX inhibitor VAS2870 equally reduced the contractile responses of arteries to α1-adrenoceptor agonist methoxamine in "Control" and "Hypoxia" pups, but its effect was more pronounced in the arteries from "Hypoxia" pups when vasocontraction was evoked by the agonist of thromboxane A2 receptors U46619. Perinatal hypoxia at the second day of life increases procontractile influence of NOX-derived ROS to the regulation of U46619-induced vasocontraction in the systemic arteries at early postnatal ontogenesis. Nothing is known about programming effects of perinatal hypoxia, including birth asphyxia, on the ROS-mediated regulation of contraction in systemic arteries of early postnatal organism. 2-h normobaric hypoxia (8% O2) in rats at the second day of life increases the procontractile contribution of NOX-produced ROS to the regulation of U46619-induced vasocontraction in the systemic arteries at early postnatal ontogenesis. This fact may serve as a risk factor for the development of various disorders at later developmental stages and should be considered regarding the therapy for newborns who have suffered neonatal asphyxia.

Aquaporin 1 confers apoptosis resistance in pulmonary arterial smooth muscle cells from the SU5416 hypoxia rat model.

Pulmonary hypertension (PH) arises from increased pulmonary vascular resistance due to contraction and remodeling of the pulmonary arteries. The structural changes include thickening of the smooth muscle layer from increased proliferation and resistance to apoptosis. The mechanisms underlying apoptosis resistance in PH are not fully understood. In cancer cells, high expression of aquaporin 1 (AQP1), a water channel, is associated with apoptosis resistance. We showed AQP1 protein was expressed in pulmonary arterial smooth muscle cells (PASMCs) and upregulated in preclinical PH models. In this study, we used PASMCs isolated from control male rats and the SU5416 plus hypoxia (SuHx) model to test the role of AQP1 in modulating susceptibility to apoptosis. We found the elevated level of AQP1 in PASMCs from SuHx rats was necessary for resistance to apoptosis and that apoptosis resistance could be conferred by increasing AQP1 in control PASMCs. In exploring the downstream pathways involved, we found AQP1 levels influence the expression of Bcl-2, with enhanced AQP1 levels corresponding to increased Bcl-2 expression, reducing the ratio of BAX to Bcl-2, consistent with apoptosis resistance. These results provide a mechanism by which AQP1 can regulate PASMC fate.

Diets containing phytobiotics, l-arginine, vitamin E and captopril modulate ascites syndrome-related genes expression in broiler chickens exposed to low ambient temperature.

Our hypothesis centred on the potential to mitigate ascites outbreaks in birds exposed to cold stress by inhibiting pulmonary artery contraction through dietary intervention. This study aimed to evaluate the effect of natural and synthetic medications on growth performance, ascites-related parameters and the expression of ascites-related genes in the lung tissue of broiler chickens under low ambient temperature. We randomly assigned 450 one-day-old male Ross 308 chicks to six dietary treatments across five replicate pens, each containing 15 chicks. The treatments included a basal diet (control), and the basal diet was supplemented with hydroalcoholic extracts of sumac (HES, 200mg/kg), Syrian mesquite (HEM, 200mg/kg), l-arginine (40% above requirement), captopril (15mg/kg) and vitamin E (100mg/kg). Diets containing HEM, l-arginine and vitamin E resulted in increased average daily gain on days 8-14 and 0-28, whereas HES showed a similar effect only during days 8-14 compared to the control diet (p<0.05). Additionally, feed additives decreased packed cell volume, left and right ventricle volumes and systolic blood pressure (p<0.05). Moreover, chickens fed the control and l-arginine diets exhibited higher levels of angiotensin converting enzyme (ACE) mRNA in lung tissue compared to those fed HES, HEM and captopril (p<0.05). Meanwhile, supplementation with HEM and l-arginine increased the expression of inducible nitric oxide synthase (iNOS) mRNA in lung tissue compared to other treatments (p<0.05). Regarding Cu/Zn-superoxide dismutase (Cu/Zn-SOD) expression, feed additives increased mRNA level in lung tissue, except for captopril (p<0.05). This study demonstrates that the plant extracts may reduce the incidence of ascites syndrome not only through their antioxidant properties but also by modulating the expression of ACE, iNOS and Cu/Zn-SOD genes.

Nfluence of extracellular acidosis on the functional contribution of KATP and TASK-1 potassium channels to the regulation of vascular tone in early postnatal ontogenesis

The activity of many proteins and, as a result, of the mechanisms of vascular tone regulation depends on pH. A decrease of pH (uncompensated acidosis), usually causes relaxation of blood vessels, which has been studied in sufficient detail for an adult, matured organism. However, the effect of acidosis on the mechanisms of vascular tone regulation in the early postnatal period remains almost completely unexplored. The aim of this work was to study the effect of extracellular metabolic acidosis on the functional contribution of KATP and TASK-1 potassium channels to the regulation of vascular tone in early postnatal period. We modeled extracellular metabolic acidosis (pH 6.8, equimolar replacement of NaHCO3 with NaCl in solution) and studied isometric contractile responses of the saphenous artery in rats aged 3–4 months and rat pups aged 12–15 days. Arterial contraction to the α1-adrenergic agonist methoxamine at pH 6.8 was reduced compared to normal pH 7.4 in both 3–4-month-old and 12–15-day-old rats. The KATP channel blocker glibenclamide did not change the arterial responses to methoxamine, neither at pH 7.4 nor at pH 6.8 in any of the age groups. The TASK-1 channel blocker AVE1231 did not alter arterial contractile responses at any pH in 3–4-month-old rats. However, in 12–15-day-old rat pups, the increase in contractile responses to methoxamine under the influence of AVE1231 was less at pH 6.8 than at pH 7.4. Thus, the results of this work demonstrate that acidosis reduces the contractile activity of the arteries of 3–4-month-old animals and animals during early postnatal ontogenesis, while in the latter, the anticontractile role of TASK-1 channels decreases, and KATP channels do not affect the regulation of vascular tone, either under normal, or at acidic pH in any of the age groups.

Alpha-linolenic acid selectively inhibits the contraction of pig coronary arteries mediated through prostanoid TP receptors

We examined the inhibitory effects of α-linolenic acid (ALA) on the contractions of pig coronary arteries. ALA concentration-dependently inhibited the contractions elicited by U46619 and prostaglandin F2α without affecting those elicited by 80 mM KCl, histamine, acetylcholine, and serotonin. ALA rightward shifted the concentration-response curve of U46619, and Schild plot analysis revealed that ALA competitively antagonized U46619. Furthermore, ALA inhibited the increase in intracellular Ca2+ concentration caused by TP receptor stimulation but not that caused by FP receptor stimulation. These results suggest that ALA behaves as a selective antagonist of TP receptors in coronary arteries.

Efektivitas Terapi Relaksasi Hand Massage Dalam Mengurangi Kecemasan Pra-Operasi Pada Pasien Kistektomi: Studi Kasus

Background: A study showed that 23.99% of patients experienced severe preoperative anxiety and had adverse effects such as increased blood pressure, contraction of arteries, tachycardia, decreased pressure in some tissues which stimulates the sympathetic nervous system which will affect the healing process, so treatment is necessary pharmacologically and non-pharmacologically. Hand massage is a non-pharmacological way to reduce anxiety. Objective: To measure the effect of hand massage relaxation therapy on anxiety levels in pre-cystectomy patients. Method: This research is a case study with nursing intervention carried out, namely hand massage relaxation therapy on the level of anxiety in Mrs. R pre-operative cystectomy patients for 3 days with a massage duration of 15 minutes and evaluation of anxiety scores using the HARS assessment. Results: The results of this study showed that there was a decrease in anxiety levels using the HARS score from scale 18 with mild anxiety on the first day and scale 7 with no anxiety on the third day. A decrease in the HARS score of 11 indicates that hand massage therapy is effective in reducing anxiety in pre-operative patients. Conclusion: These findings indicate that hand massage therapy can be an effective intervention to reduce pre-operative patient anxiety.

Estimation of differential pathlength factor from NIRS measurement in skeletal muscle

The utilization of continuous wave (CW) near-infrared spectroscopy (NIRS) device to measure non-invasively muscle oxygenation in healthy and disease states is limited by the uncertainties related to the differential path length factor (DPF). DPF value is required to quantify oxygenated and deoxygenated heme groups’ concentration changes from measurement of optical densities by NIRS. An integrated approach that combines animal and computational models of oxygen transport and utilization was used to estimate the DPF value in situ. The canine model of muscle oxidative metabolism allowed measurement of both venous oxygen content and tissue oxygenation by CW NIRS under different oxygen delivery conditions. The experimental data obtained from the animal model were integrated in a computational model of O2 transport and utilization and combined with Beer-Lambert law to estimate DPF value in contracting skeletal muscle. A 2.1 value was found for DPF by fitting the mathematical model to the experimental data obtained in contracting muscle (T3) (Med.Sci.Sports.Exerc.48(10):2013–2020,2016). With the estimated value of DPF, model simulations well predicted the optical density measured by NIRS on the same animal model but with different blood flow, arterial oxygen contents and contraction rate (J.Appl.Physiol.108:1169–1176, 2010 and 112:9–19,2013) and demonstrated the robustness of the approach proposed in estimating DPF value. The approach used can overcome the semi-quantitative nature of the NIRS and estimate non-invasively DPF to obtain an accurate concentration change of oxygenated and deoxygenated hemo groups by CW NIRS measurements in contracting skeletal muscle under different oxygen delivery and contraction rate.

Both endothelial mineralocorticoid receptor expression and hyperleptinemia are required for clinical characteristics of placental ischemia in mice.

One of the initiating events in preeclampsia (PE) is placental ischemia. Rodent models of placental ischemia do not present with vascular endothelial dysfunction, a hallmark of PE. We previously demonstrated a role for leptin in endothelial dysfunction in pregnancy in the absence of placental ischemia. We hypothesized that placental ischemia requires hyperleptinemia and endothelial mineralocorticoid receptor (ECMR) expression to induce PE-associated endothelial dysfunction in pregnant mice. We induced placental ischemia via the reduced uterine perfusion pressure (RUPP) procedure in pregnant ECMR-intact (ECMR+/+) and ECMR deletion (ECMR-/-) mice at gestational day (GD) 13. ECMR+/+ RUPP pregnant mice also received concurrent leptin infusion via miniosmotic pump (0.9 mg/kg/day). RUPP increased blood pressure via radiotelemetry and decreased fetal growth in ECMR+/+ pregnant mice. Both increases in blood pressure and reduced fetal growth were abolished in RUPP ECMR-/- mice. Placental ischemia did not decrease endothelial-dependent relaxation to acetylcholine (ACh) but increased phenylephrine (Phe) contraction in mesenteric arteries of pregnant mice, which was ablated by ECMR deletion. Addition of leptin to RUPP mice significantly reduced ACh relaxation in ECMR+/+ pregnant mice, accompanied by an increase in soluble FMS-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PLGF) ratio. In conclusion, our data indicate that high leptin levels drive endothelial dysfunction in PE and that ECMR is required for clinical characteristics of hypertension and fetal growth restriction in placental ischemia PE. Collectively, we show that both ECMR and leptin play a role to mediate PE.NEW & NOTEWORTHY Leptin is a key feature of preeclampsia that initiates vascular endothelial dysfunction in preeclampsia characterized by placental ischemia. Endothelial mineralocorticoid receptor (ECMR) deletion in placental ischemia protects pregnant mice from elevations in blood pressure and fetal growth restriction in pregnancy. Increases in leptin production mediate the key pathological feature of endothelial dysfunction in preeclampsia in rodents. ECMR activation contributes to the increase in blood pressure and fetal growth restriction in preeclampsia.

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.

Vascular contraction of umbilical arteries of pregnant women with preeclampsia.

Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium channels (Katp) has been linked to preeclampsia. Activation of Katp induces vasodilation; however, no previous study has been conducted to evaluate the effects of the inhibition of these channels in the contractility of preeclamptic arteries. Glibenclamide is an oral antihyperglycemic agent that inhibits Katp and has been widely used in vascular studies. To investigate the effects of the inhibition of Katp, umbilical arteries of preeclamptic women and women with healthy pregnancies were assessed by vascular contractility experiments, in the presence or absence of glibenclamide. The umbilical arteries were challenged with cumulative concentrations of potassium chloride (KCl) and serotonin. There were no differences between the groups concerning the maternal age and gestational age of the patients. The percentage of smokers, caucasians and primiparae per group was also similar. On the other hand, blood pressure parameters were elevated in the preeclamptic group. In addition, the preeclamptic group presented a significantly higher body mass index. The newborns of both groups presented similar APGAR scores and weights. In the presence of glibenclamide, there was an increase in the KCl-induced contractions only in vessels from the PE group, showing a possible involvement of these channels in the disorder.

Contractions Induced in Human Pulmonary Arteries by a H2S Donor, GYY 4137, Are Inhibited by Low-Frequency (20 kHz) Ultrasound.

The present study aimed to investigate the effect of a H2S donor, GYY 4137, on human pulmonary arteries and whether low-frequency ultrasound (20 kHz, 4 W/cm2) inhibits GYY 4137 contractions. Functional studies were conducted on human and rat pulmonary arteries mounted on microvascular myographs. We placed an ultrasonic gadget in the tissue organ bath to insonate the arteries with low-frequency ultrasound. To measure the effect of the low-frequency ultrasound on the entrance of extracellular Ca2+, the preparations were placed in a Ca2+-free solution, and the thromboxane agonist, U46619, and extracellular calcium were added in the presence of insonation. In isolated human pulmonary arteries, GYY 4137 induced contractions, which were most pronounced in the arteries contracted with the thromboxane analogue, U46619. The transient GYY4137 contractions were reversed by low-frequency ultrasound, a blocker of KV7 channels, XE-991 (10 µM), and glibenclamide (1 μM), a blocker of ATP-sensitive channels. Low-frequency ultrasound also inhibited the contractions induced by the smooth muscle entrance of increasing extracellular calcium concentrations. The present findings show that GYY 4137 can cause a transient contraction of pulmonary arteries in human arteries. GYY 4137 alone does not cause significant vascular contraction in rat lung arteries, but it contracts rat lung arteries precontracted with U46619. The transient contractions induced by GYY 4137 can be inhibited by low-frequency ultrasound, probably by counteracting the influx of external Ca2+. The effect of low-frequency ultrasound counteracts contraction in pulmonary arteries; therefore, a possibility could be to develop a larger device allowing treatment of patients with pulmonary hypertension.

(055) LRRC8A-VRAC Controls Superoxide Anion Flux in Diabetic Vasculogenic Erectile Dysfunction

Abstract Introduction Erectile dysfunction (ED) may be an early marker for cardiovascular diseases, and it is often associated with an hypercontractility of the corpus cavernosum (CC) as a consequence of increased reactive oxygen species (ROS), which favors the flaccid state of the penis. Leucine Rich Repeat Containing 8 (LRRC8A) Volume Regulated Anion Channels (VRACs) regulates Nox1 and modulates the extracellular production of superoxide anion (O2•-). Downregulation of LRRC8A is associated with decreased production of O2•- and we have demonstrated improved relaxation and reduced contraction of the pudendal artery in LRRC8A knockout mice. Objective We hypothesized that the role of LRRC8A in contractile responses to phenylephrine (PE) and electrical field stimulation (EFS) in the CC of diabetic mice would be exaggerated compared to that in normal mice. Methods To test this hypothesis, the CC of diabetic (dbdb-/-) mice was mounted in a myograph, and contraction elicited by PE or EFS was performed in the presence of apocynin (non-selective NOX inhibitor), GKT137831 (NOX1/4 inhibitor) and montelukast (LRRC8A inhibitor). In LRRC8A KO dbdb-/- mice, contractions to PE and EFS were obtained in the absence or in the presence of GKT137831. Results In the CC, the maximal contraction to PE was increased in diabetic animals, and in the presence of 3 mM of apocynin, the contractile response was markedly diminished in both control and diabetic mice. The LRRC8A inhibitor, montelukast, significantly reduced PE-induced contraction of the CC reaching maximal contraction of 69 + 7% and 65 + 10% in the control and diabetic group, respectively, compared to the contraction in the absence of the inhibitor. In the presence of the Nox1/Nox4 inhibitor, GKT137831, the contraction elicited by PE was reduced only in the diabetic group (68 + 9% of the maximal contraction), whereas in the control group this reduction was not significant (82 + 14% of the PE-maximal contraction). In the LRRC8A KO dbdb-/- mice, the contraction to EFS was similar to dbdb-/-, however, GKT137831 reduced the contraction to EFS with lesser magnitude of inhibition in the LRRC8A KO dbdb-/- mice (35% of inhibition) compared to dbdb-/- mice (50% of inhibition), suggesting that the participation of O2•- in the contractile response was reduced by the lack of functional LRRC8A. Conclusions LRRC8A modulates the contractile response of the CC induced by α-adrenergic stimulation and in diabetes, this may be associated with O2•- production, which plays a role in the development of ED. Inhibition of LRRC8A may be a therapeutic target to prevent hypercontractility of arteries and CC in vasculogenic ED. Disclosure No.

Computational investigation of thermal process in radiated nanofluid modulation influenced by nanoparticles (Al2O3) and molecular (H2O) diameters

Abstract The study of variety of Newtonian nanofluids subject to various physical model parameters gained much interest of engineers and scientists. Owing to their coolant and absorption characteristics, these are broadly found in chemical engineering, biomedical engineering (expansion and contraction of veins and arteries), detection of cancer cells through magnetic nanoparticles, microchips, and particularly in petroleum industry. This study focuses on investigation of nanofluid heat transfer applications inside a channel formed by expanding/contracting walls. A new heat transport model is introduced by adding the effects of nanoparticles and molecular diameters, thermal radiations, and walls permeability. Then, numerical code for the model is developed and executed to analyze the dynamics of the model from physical aspects. For expanding (${\alpha }_1 = 1.0,2.0,3.0,4.0$) and contracting (${\alpha }_1 = - 1.0, - 2.0, - 3.0, - 4.0$) walls, the velocity is examined maximum in the channel center. However, the fluid movement in the working domain is in reverse proportion for ${Re} = 1.0,3.0,5.0,7.0$. Further, high absorbent walls (${A}_1 = 0.1,0.3,0.5,0.7$) controlled the motion for both ${\alpha }_1 &amp;gt; 0$ and ${\alpha }_1 &amp;lt; 0$, respectively. The addition of thermal radiation number ${Rd} = 0.1,0.3,0.5,0.7$ played the role of catalytic parameter which imperatively increased the fluid temperature. Further, contracting walls and temperature ratio number ${\theta }_r = 0.1,0.3,0.5,0.7$ reduced the temperature and this decrease is rapid in conventional fluid.

Endothelial cell Orai1 is essential for endothelium-dependent contraction of mouse carotid arteries in normotensive and hypertensive mice.

Endothelium-dependent contraction (EDC) exists in blood vessels of normotensive animals, but is exaggerated in hypertension. An early signal in EDC is cytosolic Ca2+ rise in endothelial cells. In this study we investigated the functional role of Orai1, a major endothelial cell Ca2+ entry channel, in EDC. Hypertension model was established in WT mice by intake of L-NNA in the drinking water (0.5 g/L) for 4 weeks or osmotic pump delivery of Ang II (1.5 mg·kg-1·d-1) for 2 weeks. In TRPC5 KO mice, the concentration of L-NNA and Ang II were increased to 1 g/L or 2 mg·kg-1·d-1, respectively. Arterial segments were prepared from carotid arteries and aortas, andEDC was elicited by acetylcholine in the presence of Nω-nitro-L-arginine methyl ester. We showed that low concentration of acetylcholine (3-30 nM) initiated relaxation in phenylephrine-precontracted carotid arteries of both normotensive and hypertensive mice, while high concentration of acetylcholine (0.1-2 μM) induced contraction. Application of selective Orai1 inhibitors AnCoA4 (100 μM) or YM58483 (400 nM) had no effect on ACh-induced relaxation but markedly reduced acetylcholine-induced EDC. We found that EDC was increased in hypertensive mice compared with that of normotensive mice, which was associated with increased Orai1 expression in endothelial cells of hypertensive mice. Compared to TRPC5 and TRPV4, which were also involved in EDC, endothelial cell Orai1 had relatively greater contribution to EDC than either TRPC5 or TRPV4 alone. We identified COX-2, followed by PGF2α, PGD2 and PGE2 as the downstream signals of Orai1/TRPC5/TRPV4. In conclusion, Orai1 coordinates together with TRPC5 and TRPV4 in endothelial cells to regulate EDC responses. This study demonstrates a novel function of Orai1 in EDC in both normotensive and hypertensive mice, thus providing a general scheme about the control of EDC by Ca2+-permeable channels.

A 3D-Printed Piezoelectric Microdevice for Human Energy Harvesting for Wearable Biosensors.

The human body is a source of multiple types of energy, such as mechanical, thermal and biochemical, which can be scavenged through appropriate technological means. Mechanical vibrations originating from contraction and expansion of the radial artery represent a reliable source of displacement to be picked up and exploited by a harvester. The continuous monitoring of physiological biomarkers is an essential part of the timely and accurate diagnosis of a disease with subsequent medical treatment, and wearable biosensors are increasingly utilized for biomedical data acquisition of important biomarkers. However, they rely on batteries and their replacement introduces a discontinuity in measured signals, which could be critical for the patients and also causes discomfort. In the present work, the research into a novel 3D-printed wearable energy harvesting platform for scavenging energy from arterial pulsations via a piezoelectric material is described. An elastic thermoplastic polyurethane (TPU) film, which forms an air chamber between the skin and the piezoelectric disc electrode, was introduced to provide better adsorption to the skin, prevent damage to the piezoelectric disc and electrically isolate components in the platform from the human body. Computational fluid dynamics in the framework of COMSOL Multiphysics 6.1 software was employed to perform a series of coupled time-varying simulations of the interaction among a number of associated physical phenomena. The mathematical model of the harvester was investigated computationally, and quantification of the output energy and power parameters was used for comparisons. A prototype wearable platform enclosure was designed and manufactured using fused filament fabrication (FFF). The influence of the piezoelectric disc material and its diameter on the electrical output were studied and various geometrical parameters of the enclosure and the TPU film were optimized based on theoretical and empirical data. Physiological data, such as interdependency between the harvester skin fit and voltage output, were obtained.

A computational framework for pharmaco‐mechanical interactions in arterial walls using parallel monolithic domain decomposition methods

AbstractA computational framework is presented to numerically simulate the effects of antihypertensive drugs, in particular calcium channel blockers, on the mechanical response of arterial walls. A stretch‐dependent smooth muscle model by Uhlmann and Balzani is modified to describe the interaction of pharmacological drugs and the inhibition of smooth muscle activation. The coupled deformation‐diffusion problem is then solved using the finite element software FEDDLib and overlapping Schwarz preconditioners from the Trilinos package FROSch. These preconditioners include highly scalable parallel GDSW (generalized Dryja–Smith–Widlund) and RGDSW (reduced GDSW) preconditioners. Simulation results show the expected increase in the lumen diameter of an idealized artery due to the drug‐induced reduction of smooth muscle contraction, as well as a decrease in the rate of arterial contraction in the presence of calcium channel blockers. Strong and weak parallel scalability of the resulting computational implementation are also analyzed.

Relaxant Effects of Piperine and Piperlongumine from Piper longum Fruits on Porcine Coronary Artery.

Since ancient times, Piper longum Linn. fruits have been recognized for exhibiting various effects, including the diaphoretic effects linked to enhanced blood flow. Piperine and piperlongumine coexist in Piper longum Linn. fruits, although the cardiovascular effects of both compounds remain elusive. We investigated their action of piperine and piperlongumine in porcine coronary arteries, comparing them to the Ca2+ channel antagonist diltiazem. Piperlongumine, unlike piperine or diltiazem, concentration-dependently inhibited basal contractile tone in endothelium-denuded coronary arteries. All three compounds inhibit tonic contractions induced by high potassium chloride (KCl) concentrations. The order of relaxation potency indexed by the half-maximal effective concentration (EC50) were as follows: diltiazem > piperlongumine > piperine. These effects were not different between endothelium-intact and -denuded preparations. In endothelial-denuded preparations, pretreatment with these compounds not only inhibited KCl-induced tonic contractions attenuated calcium chloride (CaCl2)-induced ones in a Ca2+-free medium. Histamine-induced phasic contractions in a Ca2+-free medium containing intracellular Ca2+ chelator was completely suppressed by selective inositol trisphosphate receptor antagonist and piperlongumine, whereas piperine or diltiazem do not have the same effect. These findings suggest that piperine and piperlongumine similar to diltiazem cause vasorelaxation by inhibiting both KCl- and CaCl2-induced contractions in coronary arteries, possibly through the inhibition of voltage-dependent Ca2+ channels. Piperlongumine inhibits histamine-induced contractions in a Ca2+-free medium, which is associated with the intracellular Ca2+ signaling pathway, suggesting that the relaxant effect of piperlongumine differs from that of piperine.