scholarly journals SUN-LB90 Taurine Reverses Protein Malnutrition-Induced Endothelial Dysfunction of Pancreatic Vasculature

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Daniele Mendes Guizoni ◽  
Israelle Netto Freitas ◽  
Jamaira Aparecida Victorio ◽  
Everardo Magalhaes Carneiro ◽  
Ana Paula Davel
Keyword(s):  
Insulin Secretion ◽  
Endothelial Dysfunction ◽  
No Synthase ◽  
Protein Malnutrition ◽  
No Production ◽  
Pancreas Perfusion ◽  
Cardiometabolic Disorders ◽  
Pancreatic Artery ◽  
H2s Production ◽  
Endothelium Dependent Relaxation

Abstract Background: Pancreatic islets are highly vascularized and there is a correlation between endocrine pancreas function and pancreas perfusion. Protein malnutrition during early stages of development predispose to cardiovascular diseases, impaired insulin secretion and, type 2 diabetes. However, it is unknown if there are alterations in the pancreatic vasculature in response to malnutrition. Taurine (TAU) supplementation has been suggested as antihypertensive and improves endothelial function and insulin secretion in cardiometabolic disorders. Here, we investigated the effect of TAU in the vasorelaxation and endothelium-derived factors of the lieno-pancreatic artery from protein malnourished mice. Because lieno-pancreatic artery provides blood supply to pancreatic splenic lobe, a protective effect of TAU may result in cardiometabolic benefits. Methods: Post-weaned male C57Bl/6 mice fed a normal- (14%, NP) or a low-protein (6%, LP) diet for 90 days. Concomitantly, half of LP mice received 2.5% TAU in drinking water. Lieno-pancreatic artery (internal diameter ~ 160 µm) was isolated and concentration-response relaxation curves to acetylcholine (ACh), nitric oxide (NO)-donor (SNP), or hydrogen sulfide (H2S)-donor (NaHS) were performed. The involvement of NO and endothelium-derived hyperpolarization (EDH) in ACh-induced relaxation was assessed using L-NAME (NO synthase inhibitor) or KCl (to attenuate K+ efflux), respectively. Protein expression was evaluated by Western-blot; NO and H2S production by DAF-2A and WSP-1 fluorescence, respectively. Results: Endothelium-dependent relaxation to ACh was reduced in lieno-pancreatic artery from LP compared with NP group. Either KCl or L-NAME reduced ACh-induced relaxation, but only KCl abolished differences between LP and NP, suggesting that EDH rather than NO is involved in the impaired endothelium-dependent relaxation of LP. In accordance, relaxation to SNP, NO production, and endothelial NO synthase (eNOS) expression were not altered in lieno-pancreatic artery of LP group compared to NP. Because H2S has been demonstrated to have EDH activity in several blood vessels we investigated this pathway. H2S production and NaHS-induced relaxation were both reduced in lieno-pancreatic artery of LP group compared with NP. TAU treatment reversed the impaired relaxation to ACh and to NaHS, as well as significantly increased H2S production in lieno-pancreatic artery of LP group. Conclusion: Protein malnutrition resulted in endothelial dysfunction of lieno-pancreatic artery associated with an impaired production and relaxation to H2S, which was restored by TAU. Therefore, beneficial effects of TAU on lieno-pancreatic artery vasodilatory function may result in improved pancreatic islet blood flow highlighting the potential of TAU for vasculo-metabolic protection.Funding: FAPESP, CAPES.

Mesenteric arteries from stroke-prone spontaneously hypertensive rats exhibit an increase in nitric-oxide-dependent vasorelaxation

2018 ◽  
Vol 96 (8) ◽  
pp. 719-727 ◽  
Author(s):  
Brandi M. Wynne ◽  
Hicham Labazi ◽  
Victor V. Lima ◽  
Fernando S. Carneiro ◽  
R. Clinton Webb ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Vascular Reactivity ◽  
Spontaneously Hypertensive Rat ◽  
No Synthase ◽  
Mesenteric Arteries ◽  
Maximum Effect ◽  
No Production ◽  
Primary Role ◽  
Spontaneously Hypertensive

The endothelium is crucial for the maintenance of vascular tone by releasing several vasoactive substances, including nitric oxide (NO). Systemic mean arterial pressure is primarily regulated by the resistance vasculature, which has been shown to exhibit increased vascular reactivity, and decreased vasorelaxation during hypertension. Here, we aimed to determine the mechanism for mesenteric artery vasorelaxation of the stroke-prone spontaneously hypertensive rat (SHRSP). We hypothesized that endothelial NO synthase (eNOS) is upregulated in SHRSP vessels, increasing NO production to compensate for the endothelial dysfunction. Concentration–response curves to acetylcholine (ACh) were performed in second-order mesenteric arteries; we observed decreased relaxation responses to ACh (maximum effect elicited by the agonist) as compared with Wistar-Kyoto (WKY) controls. Vessels from SHRSP incubated with Nω-nitro-l-arginine methyl ester and (or) indomethacin exhibited decreased ACh-mediated relaxation, suggesting a primary role for NO-dependent relaxation. Vessels from SHRSP exhibited a significantly decreased relaxation response with inducible NO synthase (iNOS) inhibition, as compared with WKY vessels. Western blot analysis showed increased total phosphorylated NF-κB, and phosphorylated and total eNOS in SHRSP vessels. Overall, these data suggest a compensatory role for NO by increased eNOS activation. Moreover, we believe that iNOS, although increasing NO bioavailability to compensate for decreased relaxation, leads to a cycle of further endothelial dysfunction in SHRSP mesenteric arteries.

Release of EDRF and NO in ex vivo perfused aorta: inhibition by in vivo E. coli endotoxemia

1995 ◽  
Vol 268 (3) ◽  
pp. H955-H961 ◽  
Author(s):  
P. R. Myers ◽  
Q. Zhong ◽  
J. J. Jones ◽  
M. A. Tanner ◽  
H. R. Adams ◽  
...  
Keyword(s):  
Ex Vivo ◽  
No Synthase ◽  
No Production ◽  
Gram Negative ◽  
E Coli ◽  
Relaxing Factor ◽  
A 23187 ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation

Previous studies have yielded contradictory results about interrelations between endotoxin and endothelium-derived relaxing factor (EDRF). We tested the hypothesis that in vivo endotoxemia inhibits basal and/or agonist-mediated release of EDRF and nitric oxide (NO). EDRF bioactivity, NO production, and NO synthase (NOS) activity were measured in aorta from guinea pigs following 16 h of Escherichia coli endotoxemia (4 mg/kg endotoxin i.p.). Endothelium-dependent relaxation of aortic rings was studied under standard isometric conditions. Endotoxemia resulted in an 89% reduction in basal EDRF bioactivity and a 62% reduction in basal NO production in perfused aorta. EDRF bioactivity and NO production in response to the receptor-dependent agonists acetylcholine and ADP were significantly reduced in perfused aorta from endotoxemic animals. In contrast, endotoxin did not significantly inhibit EDRF bioactivity and NO production by the receptor-independent agonist A-23187. Aortic rings from endotoxemic animals likewise showed decreased vasodilator responses to acetylcholine and ADP but not to A-23187. Inducible (Ca2+ independent) NOS activity was not significantly different in control and endotoxin-treated animals. These findings indicate that prolonged endotoxemia resulted in diminution of release of EDRF, consistent with the interpretation that endotoxemia decreases basal and agonist-stimulated EDRF bioactivity and NO production with loss of endothelium-dependent vasodilator reserves during gram-negative sepsis.

scholarly journals Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Andrea Leiva ◽  
Bárbara Fuenzalida ◽  
Francisco Westermeier ◽  
Fernando Toledo ◽  
Carlos Salomón ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Plasma Cholesterol ◽  
Maternal Plasma ◽  
No Synthase ◽  
Plasma Cholesterol Level ◽  
No Production ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Potential Link ◽  
Available Information

Maternal physiological hypercholesterolemia occurs during pregnancy, ensuring normal fetal development. In some cases, the maternal plasma cholesterol level increases to above this physiological range, leading to maternal supraphysiological hypercholesterolemia (MSPH). This condition results in endothelial dysfunction and atherosclerosis in the fetal and placental vasculature. The fetal and placental endothelial dysfunction is related to alterations in the L-arginine/nitric oxide (NO) pathway and the arginase/urea pathway and results in reduced NO production. The level of tetrahydrobiopterin (BH4), a cofactor for endothelial NO synthase (eNOS), is reduced in nonpregnant women who have hypercholesterolemia, which favors the generation of the superoxide anion rather than NO (from eNOS), causing endothelial dysfunction. However, it is unknown whether MSPH is associated with changes in the level or metabolism of BH4; as a result, eNOS function is not well understood. This review summarizes the available information on the potential link between MSPH and BH4in causing human fetoplacental vascular endothelial dysfunction, which may be crucial for understanding the deleterious effects of MSPH on fetal growth and development.

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

scholarly journals Aging Additively Influences Insulin- and Insulin-Like Growth Factor-1-Mediated Endothelial Dysfunction and Antioxidant Deficiency in Spontaneously Hypertensive Rats

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 676
Author(s):  
Kunanya Masodsai ◽  
Yi-Yuan Lin ◽  
Sih-Yin Lin ◽  
Chia-Ting Su ◽  
Shin-Da Lee ◽  
...  
Keyword(s):  
Growth Factor ◽  
Endothelial Dysfunction ◽  
Spontaneously Hypertensive Rats ◽  
No Production ◽  
Organ Bath ◽  
Insulin Like Growth Factor ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Nos Inhibitors ◽  
Wistar Kyoto

This study aimed to investigate the aging-related endothelial dysfunction mediated by insulin and insulin-like growth factor-1 (IGF-1) and antioxidant deficiency in hypertension. Male spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar–Kyoto rats (WKYs) were randomly divided into 24-week-old (younger) and 48-week-old (older) groups, respectively. The endothelial function was evaluated by the insulin- and IGF-1-mediated vasorelaxation of aortic rings via the organ bath system. Serum levels of nitric oxide (NO), malondialdehyde (MDA), catalase, and total antioxidant capacity (TAC) were examined. The insulin- and IGF-1-mediated vasorelaxation was significantly impaired in both 24- and 48-week-old SHRs compared with age-matched WKYs and was significantly worse in the 48-week-old SHR than the 24-week-old SHR. After pretreatments of phosphoinositide 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the insulin- and IGF-1-mediated vasorelaxation became similar among four groups. The serum level of MDA was significantly increased, while the NO, catalase, and TAC were significantly reduced in the 48-week-old SHR compared with the 24-week-old SHR. This study demonstrated that the process of aging additively affected insulin- and IGF-1-mediated endothelial dysfunction in SHRs, which could be partly attributed to the reduced NO production and antioxidant deficiency.

Taurine treatment reverses protein malnutrition-induced endothelial dysfunction of the pancreatic vasculature: the role of hydrogen sulfide

Metabolism ◽  
2021 ◽  
pp. 154701
Author(s):  
Daniele M. Guizoni ◽  
Israelle N. Freitas ◽  
Jamaira A. Victorio ◽  
Isabela R. Possebom ◽  
Thiago R. Araujo ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Endothelial Dysfunction ◽  
Protein Malnutrition ◽  
Taurine Treatment

Decrease in ambient [Cl-] stimulates nitric oxide release from cultured rat mesangial cells

1994 ◽  
Vol 267 (1) ◽  
pp. F190-F195 ◽  
Author(s):  
H. Tsukahara ◽  
Y. Krivenko ◽  
L. C. Moore ◽  
M. S. Goligorsky
Keyword(s):  
Nitric Oxide ◽  
Mesangial Cells ◽  
Ionic Composition ◽  
Juxtaglomerular Apparatus ◽  
Cytosolic Calcium ◽  
No Synthase ◽  
Tubuloglomerular Feedback ◽  
No Production ◽  
Rapid Reduction ◽  
No Release

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. We examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]; a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we examined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production. Using an amperometric NO sensor, we found that a 13 mM decrease in ambient [Cl-] caused a rapid, Ca2+/calmodulin-dependent rise in NO release from MC. This response was not inhibitable by dexamethasone, indicating the involvement of the constitutive rather than the inducible type of NO synthase in MC. In addition, the NO release was blunted by indomethacin pretreatment, suggesting that a metabolite(s) of cyclooxygenase regulates the activation of NO synthase in MC. Our findings that small perturbations in external [Cl-] stimulate MC to release NO, a highly diffusible and rapidly acting vasodilator, provide a possible mechanism to explain the transmission of the signal for the TGF response within the JGA.

Endothelial dysfunction and arterial pressure regulation during early diabetes in mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor

2007 ◽  
Vol 293 (2) ◽  
pp. R707-R713 ◽  
Author(s):  
Sharyn M. Fitzgerald ◽  
Barbara K. Kemp-Harper ◽  
Helena C. Parkington ◽  
Geoffrey A. Head ◽  
Roger G. Evans
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Arterial Pressure ◽  
Early Stage ◽  
Mesenteric Arteries ◽  
No Production ◽  
Wild Type ◽  
Early Diabetes ◽  
Diabetes In Mice ◽  
Vehicle Treatment

We determined whether nitric oxide (NO) counters the development of hypertension at the onset of diabetes in mice, whether this is dependent on endothelial NO synthase (eNOS), and whether non-NO endothelium-dependent vasodilator mechanisms are altered in diabetes in mice. Male mice were instrumented for chronic measurement of mean arterial pressure (MAP). In wild-type mice, MAP was greater after 5 wk of Nω-nitro-l-arginine methyl ester (l-NAME; 100 mg·kg−1·day−1 in drinking water; 97 ± 3 mmHg) than after vehicle treatment (88 ± 3 mmHg). MAP was also elevated in eNOS null mice (113 ± 4 mmHg). Seven days after streptozotocin treatment (200 mg/kg iv) MAP was further increased in l-NAME-treated mice (108 ± 5 mmHg) but not in vehicle-treated mice (88 ± 3 mmHg) nor eNOS null mice (104 ± 3 mmHg). In wild-type mice, maximal vasorelaxation of mesenteric arteries to acetylcholine was not altered by chronic l-NAME or induction of diabetes but was reduced by 42 ± 6% in l-NAME-treated diabetic mice. Furthermore, the relative roles of NO and endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced vasorelaxation were altered; the EDHF component was enhanced by l-NAME and blunted by diabetes. These data suggest that NO protects against the development of hypertension during early-stage diabetes in mice, even in the absence of eNOS. Furthermore, in mesenteric arteries, diabetes is associated with reduced EDHF function, with an apparent compensatory increase in NO function. Thus, prior inhibition of NOS results in endothelial dysfunction in early diabetes, since the diabetes-induced reduction in EDHF function cannot be compensated by increases in NO production.

scholarly journals Cephalic phase insulin secretion is KATP channel independent

2013 ◽  
Vol 218 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Yusuke Seino ◽  
Takashi Miki ◽  
Wakako Fujimoto ◽  
Eun Young Lee ◽  
Yoshihisa Takahashi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Critical Role ◽  
Pancreas Perfusion ◽  
Glucose Levels ◽  
Cephalic Phase ◽  
Plasma Insulin Levels ◽  
Atropine Methyl Nitrate ◽  
Nutrient Injection

Glucose-induced insulin secretion from pancreatic β-cells critically depends on the activity of ATP-sensitive K+channels (KATPchannel). We previously generated mice lackingKir6.2, the pore subunit of the β-cell KATPchannel (Kir6.2−/−), that show almost no insulin secretion in response to glucosein vitro. In this study, we compared insulin secretion by voluntary feeding (self-motivated, oral nutrient ingestion) and by forced feeding (intra-gastric nutrient injection via gavage) in wild-type (Kir6.2+/+) andKir6.2−/−mice. Underad libitumfeeding or during voluntary feeding of standard chow, blood glucose levels and plasma insulin levels were similar inKir6.2+/+andKir6.2−/−mice. By voluntary feeding of carbohydrate alone, insulin secretion was induced significantly inKir6.2−/−mice but was markedly attenuated compared with that inKir6.2+/+mice. On forced feeding of standard chow or carbohydrate alone, the insulin secretory response was markedly impaired or completely absent inKir6.2−/−mice. Pretreatment with a muscarine receptor antagonist, atropine methyl nitrate, which does not cross the blood–brain barrier, almost completely blocked insulin secretion induced by voluntary feeding of standard chow or carbohydrate inKir6.2−/−mice. Substantial glucose-induced insulin secretion was induced in the pancreas perfusion study ofKir6.2−/−mice only in the presence of carbamylcholine. These results suggest that a KATPchannel-independent mechanism mediated by the vagal nerve plays a critical role in insulin secretion in response to nutrientsin vivo.

Arginase inhibition increases nitric oxide production in bovine pulmonary arterial endothelial cells

2004 ◽  
Vol 287 (1) ◽  
pp. L60-L68 ◽  
Author(s):  
Louis G. Chicoine ◽  
Michael L. Paffett ◽  
Tamara L. Young ◽  
Leif D. Nelin
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
No Synthase ◽  
No Production ◽  
Urea Production ◽  
Pulmonary Arterial ◽  
Factor Α ◽  
Arterial Endothelial Cells ◽  
Regular Medium ◽  
Necrosis Factor

Nitric oxide (NO) is produced by NO synthase (NOS) from l-arginine (l-Arg). Alternatively, l-Arg can be metabolized by arginase to produce l-ornithine and urea. Arginase (AR) exists in two isoforms, ARI and ARII. We hypothesized that inhibiting AR with l-valine (l-Val) would increase NO production in bovine pulmonary arterial endothelial cells (bPAEC). bPAEC were grown to confluence in either regular medium (EGM; control) or EGM with lipopolysaccharide and tumor necrosis factor-α (L/T) added. Treatment of bPAEC with L/T resulted in greater ARI protein expression and ARII mRNA expression than in control bPAEC. Addition of l-Val to the medium led to a concentration-dependent decrease in urea production and a concentration-dependent increase in NO production in both control and L/T-treated bPAEC. In a second set of experiments, control and L/T bPAEC were grown in EGM, EGM with 30 mM l-Val, EGM with 10 mM l-Arg, or EGM with both 10 mM l-Arg and 30 mM l-Val. In both control and L/T bPAEC, treatment with l-Val decreased urea production and increased NO production. Treatment with l-Arg increased both urea and NO production. The addition of the combination l-Arg and l-Val decreased urea production compared with the addition of l-Arg alone and increased NO production compared with l-Val alone. These data suggest that competition for intracellular l-Arg by AR may be involved in the regulation of NOS activity in control bPAEC and in response to L/T treatment.

Sign in / Sign up

Export Citation Format

Share Document