Sepiapterin Improves Vascular Reactivity and Insulin-Stimulated Glucose in Wistar Rats

In the vasculature, sedentary behavior leads to endothelial abnormalities, resulting in elevated cardiovascular disease risk. Endothelial nitric oxide synthase (eNOS) aberrations characterize endothelial dysfunction; eNOS also regulates mitochondrial function. We hypothesized that sepiapterin (a precursor to eNOS cofactor tetrahydrobiopterin (BH4)) supplementation would improve endothelium-dependent vascular relaxation in sedentary animals via modulation of NOS function and mitochondrial activity. Sedentary male Wistar rats were fed ad libitum for a total of 10 weeks. Sepiapterin was administered in diet during the final 5 weeks. Intraperitoneal insulin and glucose tolerance tests (IP-ITT/IP-GTT) were conducted at baseline and endpoint. Aorta was assessed for vasoreactivity and mitochondrial respiration. Insulin tolerance, determined by IP-ITT, significantly improved in rats treated with sepiapterin (p<0.05, interaction of time and treatment). Acetylcholine- (ACh-) driven vasodilation was significantly greater in aorta from sepiapterin-treated rats as compared with control (76.4% versus 54.9% of phenylephrine contraction at 20 μM ACh, p<0.05). Sepiapterin treatment resulted in significantly elevated state 3 (9.00 oxygen pmol/sec∗mg versus 8.17 oxygen pmol/sec∗mg, p<0.05) and 4 (7.28 oxygen pmol/sec∗mg versus 5.86 oxygen pmol/sec∗mg, p<0.05) aortic mitochondrial respiration with significantly lower respiratory control ratio (p<0.05) during octanoylcarnitine-driven respiration. Vasodilation and insulin sensitivity were improved through targeting NOS via sepiapterin supplementation.

Download Full-text

Oxidative stress, mitochondrial respiration, and glycemic control: Clues from chronic supplementation with Cr3+ or As3+ to male wistar rats

Nutrition ◽

10.1016/s0899-9007(97)00338-9 ◽

1997 ◽

Vol 13 (11-12) ◽

pp. 965-970 ◽

Cited By ~ 22

Author(s):

JoséM. Cobo ◽

Miguel Castiñeira

Keyword(s):

Oxidative Stress ◽

Glycemic Control ◽

Mitochondrial Respiration ◽

Wistar Rats ◽

Male Wistar Rats

Download Full-text

Hyperoxia blunts acute hypoxia- and PGF2α-induced pulmonary vasoconstriction in chronically hypoxic rats

Physiological Research ◽

10.33549/physiolres.931878 ◽

2009 ◽

pp. 917-920

Author(s):

M Žaloudíková ◽

M Vízek ◽

J Herget

Keyword(s):

Wistar Rats ◽

Vascular Reactivity ◽

Chronic Hypoxia ◽

Acute Hypoxia ◽

Gas Mixture ◽

Pulmonary Vasoconstriction ◽

Radical Production ◽

Male Wistar Rats ◽

Lung Preparation

We investigated the influence of oxygenation of in vitro lung preparation on the pulmonary vascular reactivity. Small pulmonary vessels isolated from adult male Wistar rats exposed for 4 days to hypoxia (FiO2 = 0.1, group CH) were compared with those of normoxic controls (group N). The bath in the chamber of small vessel myograph was saturated with gas mixture containing either 21 % or 95 % of O2 with 5 % CO2 and we measured the reactions of vessels to acute hypoxic challenge with 0 % O2 or to PGF2α. We did not observe any difference of the contractile responses between both groups when the normoxic conditions were set in the bath. When the bath oxygenation was increased to 95 % O2, the contractions induced by hypoxic challenge and PGF2α decreased in chronically hypoxic rats and did not change in normoxic controls. We hypothesize that reduced reactivity of vessels from hypoxic rats in hyperoxia results from the effect of chronic hypoxia on Ca2+ signaling in the vascular smooth muscle, which is modulated by increased free radical production during the exposure to chronic hypoxia and further hyperoxia.

Download Full-text

Vascular α1-Adrenergic Receptor Responsiveness in Masked Hypertension

American Journal of Hypertension ◽

10.1093/ajh/hpaa032 ◽

2020 ◽

Vol 33 (8) ◽

pp. 713-717 ◽

Cited By ~ 1

Author(s):

Yuichiro Yano ◽

Anthony J Viera ◽

Alan L Hinderliter ◽

Lana L Watkins ◽

James A Blumenthal ◽

...

Keyword(s):

Blood Pressure ◽

Vascular Reactivity ◽

Disease Risk ◽

Blood Pressure Monitoring ◽

Cardiovascular Disease Risk ◽

Masked Hypertension ◽

Hypertension Clinic ◽

Sustained Hypertension ◽

Middle Aged Adults ◽

Multivariable Adjustment

Abstract BACKGROUND Masked hypertension (nonhypertensive in the clinic setting but hypertensive outside the clinic during wakefulness) is characterized by increased blood pressure in response to physical and emotional stressors that activate the sympathetic nervous system (SNS). However, no studies have assessed vascular reactivity to a pharmacological SNS challenge in individuals with masked hypertension. METHODS We analyzed data from 161 adults aged 25 to 45 years (mean ± standard deviation age 33 ± 6 years; 48% were African American and 43% were female). Participants completed ambulatory blood pressure monitoring, and a standardized α 1-adrenergic agonist phenylephrine test that determines the dose of phenylephrine required to increase a participant’s mean arterial pressure by 25 mm Hg (PD25). RESULTS Twenty-one participants were considered to have masked hypertension (clinic systolic blood pressure (SBP) <140 and diastolic blood pressure (DBP) <90 mm Hg but awake SBP ≥135 or DBP ≥85 mm Hg), 28 had sustained hypertension (clinic SBP ≥140 or DBP ≥90 mm Hg and awake SBP ≥135 or DBP ≥85 mm Hg), and 106 had sustained normotension (clinic SBP <140 and DBP <90 mm Hg and awake SBP <135 and DBP <85 mm Hg). After multivariable adjustment, the mean (±SE) PD25 was less in participants with masked hypertension compared with their counterparts with sustained normotension (222.1 ± 33.2 vs. 328.7 ± 15.0; P = 0.012), but similar to that observed in subjects with sustained hypertension (254.8 ± 31.0; P =0.12). CONCLUSIONS Among young and middle-aged adults, masked hypertension is associated with increased vascular reactivity to a SNS challenge, which may contribute to elevated awake BPs as well as to increased cardiovascular disease risk.

Download Full-text

Enhanced Na+, K+-ATPase activity and endothelial modulation decrease phenylephrine-induced contraction in aorta from ouabain-treated normotensive and hypertensive rats

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0058 ◽

2014 ◽

Vol 18 (2) ◽

Cited By ~ 1

Author(s):

Ana Paula Davel ◽

Gisele Kruger Couto ◽

Camilla Ferreira Wenceslau ◽

Emilia Cristina Peres ◽

Fabiano Elias Xavier ◽

...

Keyword(s):

Protein Expression ◽

Wistar Rats ◽

Vascular Reactivity ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Vasoconstrictor Response ◽

Adrenergic Response ◽

Male Wistar Rats ◽

Cox 2

AbstractThe purpose of this study was to compare the effect of long-term ouabain treatment on the vascular reactivity and NaMale Wistar rats were treated with ouabain (~8.0 µg/day, subcutaneously) or vehicle for 5 and 20 weeks, and spontaneously hypertensive rats (SHRs) for 5 weeks. Vasoconstrictor response to phenylephrine (10The phenylephrine-induced contraction was reduced, whereas the relaxation to KCl was enhanced in the aorta of ouabain-treated Wistar rats and SHRs. In both strains, endothelial modulation of α-adrenergic response was enhanced, related to an increased NO and reduced COX-derived vasoconstrictor factor modulation. Aortas from 20-week ouabain-treated Wistar rats showed reduced COX-2 and enhanced eNOS protein expression. In SHRs, 5-week ouabain treatment reduced COX-2 and increased nNOS protein expression.The results suggest that long-term ouabain treatment reduces the α-adrenergic response of aorta from normotensive rats and SHRs, associated with an increase of NO synthesis, reduced COX-2-derived vasoconstrictor factors, and enhanced ouabain-sensitive Na

Download Full-text

Peptide fragments of bradykinin show unexpected biological activity not mediated by B1 or B2 receptors

10.22541/au.161194577.79249414/v1 ◽

2021 ◽

Author(s):

Igor Souza-Silva ◽

Cristiane de Paula ◽

Lucas Bolais-Ramos ◽

Anderson Santos ◽

Filipe da Silva ◽

...

Keyword(s):

Biological Activity ◽

Adult Male ◽

Wistar Rats ◽

Vascular Reactivity ◽

Biological Activities ◽

No Production ◽

Peptide Fragments ◽

Kinin System ◽

Male Wistar Rats

Background and purpose: Bradykinin [BK-(1-9)] is an endogenous nonapeptide involved in multiple physiological and pathological processes. A long-held belief is that peptide fragments of BK-(1-9) are biologically inactive. Here, we have tested the biological activities of BK-(1-9) and two major peptide fragments in human and animal systems. Experimental Approach: Levels of BK peptides in male Wistar rat plasma were quantified by mass spectrometric methods. Nitric oxide was quantified in human, mouse and rat cells, and loaded with DAF-FM. We used aortic rings from adult male Wistar rats to test vascular reactivity. Changes in blood pressure and heart rate were measured in conscious adult male Wistar rats. Key results: Plasma levels of BK-(1-7) and BK-(1-5) in rats were increased following infusion of BK-(1-9). All tested peptides induced NO production in all cell types tested. However, unlike BK-(1-9), NO production elicited by BK-(1-7) or BK-(1-5) was not inhibited by B or B receptor antagonists. BK-(1-7) or BK-(1-5) also induced concentration-dependent vasorelaxation of aortic rings, without involving B or B receptors. In vivo, either intravenous or intra-arterial administration of BK-(1-7) or BK-(1-5) induced similar hypotension response. Conclusions and implications: BK-(1-7) and BK-(1-5) are endogenous peptides present in plasma. They are formed, at least partially, through the BK-(1-9) proteolysis. BK-related peptide fragments show biological activity, not mediated by B or B receptors. These BK-fragments could constitute new, active components of the kallikrein-kinin system.

Download Full-text

Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502008000700012 ◽

2008 ◽

Vol 23 (suppl 1) ◽

pp. 66-71 ◽

Cited By ~ 4

Author(s):

Rafael Kemp ◽

Orlando de Castro-e-Silva ◽

José Sebastião dos Santos ◽

Ajith Kumar Sankarankutty ◽

Rodrigo Borges Correa ◽

...

Keyword(s):

Oxygen Consumption ◽

Statistical Analysis ◽

Bile Duct ◽

Mitochondrial Respiration ◽

Respiratory Control ◽

Cellular Respiration ◽

Sham Operation ◽

Significant Drop ◽

Stage 4 ◽

Male Wistar Rats

PURPOSE: The objective of the present study was to evaluate the capacity of the myocardium for energy production by the analysis of mitochondrial respiration in rats with jaundice submitted to bile duct ligature. METHODS: Sixteen male Wistar rats were divided into 2 Groups: Group SO submitted to nontherapeutic laparotomy (sham operation) and Group IC (icteric group) submitted to bile duct ligature. After 7 days, laparotomy was again performed in all animals for cardiac muscle extraction and analysis. Mitochondrial oxygen consumption was determined by stage 3 velocity and stage 4 velocity. The respiratory control ratio (RCR) was obtained by the ratio of stage 3 to stage 4 velocity. Statistical analysis was performed by the Mann-Whitney test, with the level of significance set at 5% (p<0.05). RESULTS: Statistical analysis revealed a significant drop in oxygen consumption during stage 3 mitochondrial respiration in group IC compared with SO, whereas the values obtained during stage 4 were basically identical for the two groups. Likewise, RCR values exhibited a significant reduction. CONCLUSION: The cellular respiration of the "jaundiced heart" is depressed. This was demonstrated by the reduced capacity of cardiac mitochondria to consume oxygen and synthesize ATP, supporting the idea of a latent cardiac impairment responsible for the hemodynamic decompensation occurring during cholestasis.

Download Full-text

Effects of Moringa oleifera leaf powder on metabolic syndrome induced in male Wistar rats: a preliminary study

Journal of International Medical Research ◽

10.1177/0300060518781726 ◽

2018 ◽

Vol 46 (8) ◽

pp. 3327-3336 ◽

Cited By ~ 10

Author(s):

Marisa López ◽

Mónica Ríos-Silva ◽

Miguel Huerta ◽

Yolitzy Cárdenas ◽

Jaime Alberto Bricio-Barrios ◽

...

Keyword(s):

Glucose Tolerance ◽

Wistar Rats ◽

Moringa Oleifera ◽

Fasting Glucose ◽

Abdominal Circumference ◽

Control Group ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Insulin Tolerance ◽

Male Wistar Rats

Objective To evaluate the preventive effects of Moringa oleifera on metabolic syndrome (MS) in male Wistar rats. Methods MS was induced by feeding rats a high-fat diet and drinking water containing 10% fructose for 6 weeks. In the preventive group, M. oleifera was orally administered for 3 weeks prior to the induction of MS, while in the treatment group, M. oleifera was administered for 3 weeks after the onset of MS. The treatment groups were compared with a control group of untreated rats with induced MS. Fasting glucose, oral glucose tolerance, insulin tolerance, total cholesterol, triglycerides, abdominal circumference, and systolic and diastolic blood pressure were measured before and after MS induction and/or M. oleifera treatment. Results After the induction of MS, the control group had higher fasting glucose levels than the preventive group. No significant differences were observed in insulin tolerance, oral glucose tolerance, cholesterol, triglycerides, abdominal circumference, or systolic or diastolic blood pressure. Compared with untreated controls, rats in the treatment group had significantly improved glucose tolerance, triglycerides, and abdominal circumference. Conclusions M. oleifera treatment attenuates MS in Wistar rats.

Download Full-text

Cardiovascular Disease Risk Factors and Platelet Mitochondrial Function in School Age Children (P21-059-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz041.p21-059-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Eva Diaz Fuentes ◽

Sean Adams ◽

Catarina Young ◽

Judith Weber ◽

Elisabet Borsheim

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Fatty Acid ◽

Mitochondrial Function ◽

Mitochondrial Respiration ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

School Age Children ◽

Acid Oxidation ◽

School Age

Abstract Objectives Platelets (PL) are an accessible source of human mitochondria. Thus, PL are advantageous when studying mitochondrial function in vulnerable populations. The objective of this study was to measure the association between parameters of PL mitochondrial respiration and markers of cardiovascular disease risk [adiposity, fitness and blood pressure (BP)] in a sub-sample of school age children participants of a larger study called Arkansas Active Kids. Methods After overnight fasting, body composition (DXA), VO2peak (incremental cycle ergometer test), resting BP, and mitochondrial function of permeabilized platelets (high-resolution respirometry) were measured in 46 children. Routine respiration (R), fatty acid oxidation (F = octanoylcarnitine + ADP + malate), respiratory stimulation by simultaneous action of F plus NADH-linked complex (C) I substrates (F&CI = pyruvate, malate and glutamate), succinate (F&CI&CII), and glycerolphosphate (F&CI&CII&GpDH) were measured. Noncoupled electron transfer capacity (ETE, FCCP), CIIE&GpDHE respiration (rotenone), residual oxygen consumption (ROX, antimycin) and CIV activity were also measured. Flux control ratios were computed by normalizing to ET capacity in the presence of NADH-linked substrates. Data presented as mean ± SD and Spearman correlations (Rho). Results Children were 9 ± 1 years with an average BMI percentile (BMIp) of 59 ± 30, and % fat mass (%FM) of 33 ± 6% (range: 25 to 49%). Ten children (22%) had either elevated or stage 1 hypertension as defined by the American Academy of Pediatrics. Diastolic BP percentile, VO2peak (ml·kg−1 fat-free-mass−1), BMIP, and % fat mass (%FM) did not correlate with any parameter of platelet mitochondrial respiration. However, visceral fat area (cm2) correlated with FAO (Rho = 0.35, P = 0.017) and F&CI (Rho = 0.30, P = 0.043) while systolic BP correlated with F&CI&CII&GpDH (Rho = 0.31, P = 0.037) and ETE (Rho = 0.43, P = 0.003). Conclusions In this preliminary analysis, PL fatty acid oxidation of school-age children increased with increasing visceral adiposity while the convergent electron flow through the Q-junction increased with increasing systolic blood pressure. Funding Sources USDA 59-6250-4-001; NIH P20GM109096. USDA/ARS Project 6026-51000-010-05S.

Download Full-text