Indole-3-propionic acid, a tryptophan-derived bacterial metabolite, increases blood pressure via cardiac and vascular mechanisms in rats

2021 ◽  
Author(s):  
Piotr Konopelski ◽  
Dawid Chabowski ◽  
Marta Aleksandrowicz ◽  
Ewa Kozniewska ◽  
Piotr Podsadni ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Propionic Acid ◽  
Metabolic Activity ◽  
Ex Vivo ◽  
Circulatory System ◽  
Cardiovascular Responses ◽  
Gut Bacteria ◽  
Qtc Interval ◽  
Resistance Arteries ◽  
Wistar Kyoto

Objectives. Recent evidence suggests that gut bacteria-derived metabolites interact with the cardiovascular system and alter blood pressure (BP) in mammals. Here, we evaluated the effect of indole-3-propionic acid (IPA), a gut bacteria-derived metabolite of tryptophan, on the circulatory system. Methods. Arterial BP, electrocardiographic and echocardiographic (ECHO) parameters were recorded in male, anesthetized, 12-week-old Wistar-Kyoto rats at baseline and after intravenous administration of either IPA or vehicle. In additional experiments, rats were pretreated with prazosin or pentolinium to evaluate the involvement of the autonomic nervous system in cardiovascular responses to IPA. IPA's concentrations were measured using UHPLC-MS. The reactivity of endothelium-intact and -denuded mesenteric resistance arteries was tested. Cells' viability and LDH cytotoxicity assays were performed on cultured cardiomyocytes. Results. IPA increased BP with a concomitant bradycardic response but no significant change in QTc interval. The pretreatment with prazosin and pentolinium reduced the hypertensive response. ECHO showed increased contractility of the heart after the administration of IPA. Ex vivo, IPA constricted pre-dilated and endothelium-denuded mesenteric resistance arteries and increased metabolic activity of cardiomyocytes. Conclusions. IPA increases BP via cardiac and vascular mechanisms in rats. Furthermore, IPA increases cardiac contractility and metabolic activity of cardiomyocytes. Our study suggests that IPA may act as a mediator between gut microbiota and the circulatory system.

Abstract 12689: Cardiovascular Responses to Energy Drinks in a Healthy Population: The C-energy Study

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Teri M Kozik ◽  
Mouchumi Bhattacharyya ◽  
Teresa T Nguyen ◽  
Therese F Connolly ◽  
Walther Chien ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Vital Signs ◽  
Cardiovascular Responses ◽  
Energy Drinks ◽  
Energy Drink ◽  
Emergency Department Visits ◽  
Qtc Interval ◽  
Cardiac Responses ◽  
Energy Drink Consumption

Introduction: Energy drinks are presumed to enhance energy, physical endurance, mood, and boost metabolism. Serious health risks have been reported with energy drink consumption such as myocardial infarction, cardiac arrest, stroke, seizures, and arrhythmias. More than 20,000 emergency department visits related to energy drink consumption were reported in 2011. Little is known about the possible pathophysiological mechanisms and adverse events associated with energy drinks. Unlike the tobacco and alcohol industry, there are limited restrictions regulating the purchasing and marketing of these drinks. Purpose: To determine if consumption of energy drinks alter; vital signs (blood pressure, temperature), electrolytes (magnesium, potassium, calcium), activated bleeding time (ACT), or cardiac responses measured with a 12-lead electrocardiographic (ECG) Holter. Method: Subjects consumed two-16 ounce cans of an energy drink within one hour and remained in the lab where data was collected at base line (BL) and then during four hours post consumption (PC). Vital signs were taken every 30 minutes; blood samples were collected at BL, one, two and four hours PC and ECG data was collected throughout the entire study period. Paired students t-test and a corresponding non-parametric test (Wilcoxon signed rank) were used for analysis of the data. Results: Fourteen healthy young subjects were recruited (mean age 28.6 years). Systolic blood pressure (BL=132, ±7.83; PC= 151, ±11.21; p=.001); QTc interval (BL=423, ±22.74; PC=503, ±24.56; p<.001); magnesium level (BL 2.04, ± 0.09; PC=2.13, ±0.15; p=.05); and calcium level (BL=9.31, ±.28; PC=9.52, ±.22; p=.018) significantly increased from BL. While potassium and ACT fluctuated (increase and decrease) no significant changes were observed. Eight of the fourteen subjects (57%) developed a QTc >500 milliseconds PC. Conclusions: In our sample, consumption of energy drinks increased systolic blood pressure, serum magnesium and calcium, and resulted in repolarization abnormalities. Because these physiological responses can lead to arrhythmias and other abnormal cardiac responses, further study in a larger sample is needed to determine the effects and possible consequences of energy drink consumption.

Reciprocal rat chromosome 2 congenic strains reveal contrasting blood pressure and heart rate QTL

2002 ◽  
Vol 10 (3) ◽  
pp. 199-210 ◽  
Author(s):  
Adamu Alemayehu ◽  
Laura Breen ◽  
Drahomira Krenova ◽  
Morton P. Printz
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Spontaneously Hypertensive Rat ◽  
Cardiovascular Responses ◽  
Chromosome 2 ◽  
Spontaneously Hypertensive ◽  
Congenic Strains ◽  
Multiple Blood ◽  
Wistar Kyoto ◽  
Chromosome Segments

Evidence exists implying multiple blood pressure quantitative trait loci (QTL) on rat chromosome 2. To examine this possibility, four congenic strains and nine substrains were developed with varying size chromosome segments introgressed from the spontaneously hypertensive rat (SHR/lj) and normotensive Wistar-Kyoto rat (WKY/lj) onto the reciprocal genetic background. Cardiovascular phenotyping was conducted with telemetry over extended periods during standard salt (0.7%) and high-salt (8%) diets. Our results are consistent with at least three independent pressor QTL: transfer of SHR/lj alleles to WKY/lj reveals pressor QTL within D2Rat21-D2Rat27 and D2Mgh10-D2Rat62, whereas transfer of WKY/lj D2Rat161-D2Mit8 to SHR/lj reveals a depressor locus. Our results also suggest a depressor QTL in SHR/lj located within D2Rat161-D2Mgh10. Introgressed WKY/lj segments also reveal a heart rate QTL within D2Rat40-D2Rat50 which abolished salt-induced bradycardia, dependent upon adjoining SHR/lj alleles. This study confirms the presence of multiple blood pressure QTL on chromosome 2. Taken together with our other studies, we conclude that rat chromosome 2 is rich in alleles for cardiovascular and behavioral traits and for coordinated coupling between behavior and cardiovascular responses.

MO094SALT INFLUENCES UROMODULIN EXCRETION INDEPENDENT OF BLOOD PRESSURE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sheon Mary ◽  
Philipp Boder ◽  
Giacomo Rossitto ◽  
Lesley Graham ◽  
Kayley Scott ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endoplasmic Reticulum ◽  
Direct Effect ◽  
Ex Vivo ◽  
Mrna Levels ◽  
Salt Loading ◽  
Spontaneously Hypertensive ◽  
Risk Variants ◽  
Wistar Kyoto

Abstract Background and Aims Uromodulin (UMOD) is the most abundant renal protein secreted into urine by the thick ascending epithelial (TAL) cells of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants and hypertension. Studies on UMOD overexpressing transgenic mice have shown that UMOD increases the tubular salt reabsorption via enhanced NKCC2 activity. We aimed to dissect the effect of salt-loading and blood pressure on the excretion of UMOD. Method Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats (n=8/sex/strain) were maintained on 1% NaCl for three weeks. Salt-loaded SHRSP were treated with nifedipine. Tubule isolation and ex vivo incubation with nifedipine were used to assess its direct effect on TAL. Results Urinary UMOD excretion was significantly reduced after salt loading in both strains (figure). In salt-loaded SHRSP, nifedipine treatment reduced blood pressure and urinary UMOD excretion. The reductions in urinary UMOD excretion were dissociated from unchanged kidney UMOD protein and mRNA levels, however, were associated with UMOD endoplasmic reticulum accumulation, thus suggesting secretion as a key regulatory step. Ex vivo experiments with TAL tubules showed that nifedipine did not have a direct effect on UMOD secretion. Conclusion Our data suggest a direct effect of salt on UMOD secretion independent of blood pressure and a potential role of endoplasmic reticulum stress on the control of UMOD secretion. The role of UMOD as a cardiovascular risk marker deserves mechanistic reappraisal and further investigations based on our findings.

scholarly journals Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors

2019 ◽  
Vol 471 (11-12) ◽  
pp. 1441-1453 ◽  
Author(s):  
Maksymilian Onyszkiewicz ◽  
Marta Gawrys-Kopczynska ◽  
Piotr Konopelski ◽  
Marta Aleksandrowicz ◽  
Aneta Sawicka ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vagus Nerve ◽  
Arterial Blood Pressure ◽  
Butyric Acid ◽  
Ex Vivo ◽  
Fold Increase ◽  
Hypotensive Effect ◽  
Gut Bacteria ◽  
Nitric Oxide Synthase Inhibitor ◽  
Arterial Blood

AbstractButyric acid (BA) is a short-chain fatty acid (SCFA) produced by gut bacteria in the colon. We hypothesized that colon-derived BA may affect hemodynamics. Arterial blood pressure (BP) and heart rate (HR) were recorded in anesthetized, male, 14-week-old Wistar rats. A vehicle, BA, or 3-hydroxybutyrate, an antagonist of SCFA receptors GPR41/43 (ANT) were administered intravenously (IV) or into the colon (IC). Reactivity of mesenteric (MA) and gracilis muscle (GMA) arteries was tested ex vivo. The concentration of BA in stools, urine, portal, and systemic blood was measured with liquid chromatography coupled with mass spectrometry. BA administered IV decreased BP with no significant effect on HR. The ANT reduced, whereas L-NAME, a nitric oxide synthase inhibitor, did not affect the hypotensive effect of BA. In comparison to BA administered intravenously, BA administered into the colon produced a significantly longer decrease in BP and a decrease in HR, which was associated with a 2–3-fold increase in BA colon content. Subphrenic vagotomy and IC pretreatment with the ANT significantly reduced the hypotensive effect. Ex vivo, BA dilated MA and GMA. In conclusion, an increase in the concentration of BA in the colon produces a significant hypotensive effect which depends on the afferent colonic vagus nerve signaling and GPR41/43 receptors. BA seems to be one of mediators between gut microbiota and the circulatory system.

scholarly journals Circumventricular Organ Apelin Receptor Knockdown Decreases Blood Pressure and Sympathetic Drive Responses in the Spontaneously Hypertensive Rat

2021 ◽  
Vol 12 ◽  
Author(s):  
Philip R. Griffiths ◽  
Stephen J. Lolait ◽  
Julian F. R. Paton ◽  
Anne-Marie O’Carroll
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Cardiovascular Response ◽  
Cardiovascular Responses ◽  
Circumventricular Organs ◽  
Major Question ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Apelin Receptor ◽  
Wistar Kyoto

The central site(s) mediating the cardiovascular actions of the apelin-apelin receptor (APJ) system remains a major question. We hypothesized that the sensory circumventricular organs (CVOs), interfacing between the circulation and deeper brain structures, are sites where circulating apelin acts as a signal in the central nervous system to decrease blood pressure (BP). We show that APJ gene (aplnr) expression was elevated in the CVOs of spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto (WKY) controls, and that there was a greater mean arterial BP (MABP) decrease following microinjection of [Pyr1]apelin-13 to the CVOs of SHRs compared to WKY rats. Lentiviral APJ-specific-shRNA (LV-APJ-shRNA) was used to knockdown aplnr expression, both collectively in three CVOs and discretely in individual CVOs, of rats implanted with radiotelemeters to measure arterial pressure. LV-APJ-shRNA-injection decreased aplnr expression in the CVOs and abolished MABP responses to microinjection of [Pyr1]apelin-13. Chronic knockdown of aplnr in any of the CVOs, collectively or individually, did not affect basal MABP in SHR or WKY rats. Moreover, knockdown of aplnr in any of the CVOs individually did not affect the depressor response to systemic [Pyr1]apelin-13. By contrast, multiple knockdown of aplnr in the three CVOs reduced acute cardiovascular responses to peripheral [Pyr1]apelin-13 administration in SHR but not WKY rats. These results suggest that endogenous APJ activity in the CVOs has no effect on basal BP but that functional APJ in the CVOs is required for an intact cardiovascular response to peripherally administered apelin in the SHR.

Cardiovascular Responses to Muscle Stretching: A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Ewan Thomas ◽  
Marianna Bellafiore ◽  
Ambra Gentile ◽  
Antonio Paoli ◽  
Antonio Palma ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiovascular System ◽  
Vascular Function ◽  
Meta Analysis ◽  
Random Effect ◽  
Cardiovascular Responses ◽  
Qualitative Description ◽  
Cross Sectional ◽  
Quantitative Synthesis

AbstractThe aim of this study will be to review the current body of literature to understand the effects of stretching on the responses of the cardiovascular system. A literature search was performed using the following databases: Scopus, NLM Pubmed and ScienceDirect. Studies regarding the effects of stretching on responses of the cardiovascular system were investigated. Outcomes regarded heart rate(HR), blood pressure, pulse wave velocity (PWV of which baPWV for brachial-ankle and cfPWV for carotid-femoral waveforms), heart rate variability and endothelial vascular function. Subsequently, the effects of each outcome were quantitatively synthetized using meta-analytic synthesis with random-effect models. A total of 16 studies were considered eligible and included in the quantitative synthesis. Groups were also stratified according to cross-sectional or longitudinal stretching interventions. Quality assessment through the NHLBI tools observed a “fair-to-good” quality of the studies. The meta-analytic synthesis showed a significant effect of d=0.38 concerning HR, d=2.04 regarding baPWV and d=0.46 for cfPWV. Stretching significantly reduces arterial stiffness and HR. The qualitative description of the studies was also supported by the meta-analytic synthesis. No adverse effects were reported, after stretching, in patients affected by cardiovascular disease on blood pressure. There is a lack of studies regarding vascular adaptations to stretching.

scholarly journals Novel role of endothelial BKCa channels in altered vasoreactivity following hypoxia

2010 ◽  
Vol 299 (5) ◽  
pp. H1439-H1450 ◽  
Author(s):  
Jennifer M. Hughes ◽  
Melissa A. Riddle ◽  
Michael L. Paffett ◽  
Laura V. Gonzalez Bosc ◽  
Benjimen R. Walker
Keyword(s):  
Ex Vivo ◽  
Barometric Pressure ◽  
Channel Blockers ◽  
Channel Activity ◽  
Resistance Arteries ◽  
Bkca Channels ◽  
Oxide Synthase ◽  
Increased Activity ◽  
Small Conductance

The systemic vasculature exhibits attenuated vasoconstriction following hypobaric chronic hypoxia (CH) that is associated with endothelium-dependent vascular smooth muscle (VSM) cell hyperpolarization. We hypothesized that increased activity of endothelial cell (EC) large-conductance, calcium-activated potassium (BKCa) channels contributes to this response. Gracilis resistance arteries from hypobaric CH (barometric pressure = 380 mmHg for 48 h) rats demonstrated reduced myogenic reactivity and hyperpolarized VSM membrane potential ( Em) compared with controls under normoxic ex vivo conditions. These differences were eliminated by endothelial disruption. In the presence of cyclooxygenase and nitric oxide synthase inhibition, combined intraluminal administration of the intermediate and small-conductance, calcium-activated K+ channel blockers TRAM-34 and apamin was without effect on myogenic responsiveness and VSM Em in both groups; however, these variables were normalized in CH arteries by intraluminal administration of the BKCa inhibitor iberiotoxin (IBTX). Basal EC Em was hyperpolarized in arteries from CH rats compared with controls and was restored by IBTX, but not by TRAM-34/apamin. K+ channel blockers were without effect on EC basal Em in controls. Similarly, IBTX blocked acetylcholine-induced dilation in arteries from CH rats, but was without effect in controls, whereas TRAM-34/apamin eliminated dilation in controls. Acetylcholine-induced EC hyperpolarization and calcium responses were inhibited by IBTX in CH arteries and by TRAM-34/apamin in controls. Patch-clamp experiments on freshly isolated ECs demonstrated greater K+ current in cells from CH rats that was normalized by IBTX. IBTX was without effect on K+ current in controls. We conclude that hypobaric CH induces increased endothelial BKCa channel activity that contributes to reduced myogenic responsiveness and EC and VSM cell hyperpolarization.

scholarly journals Plasticity in breathing and arterial blood pressure following acute intermittent hypercapnic hypoxia in infant rat pups with a partial loss of 5-HT neurons

2015 ◽  
Vol 309 (10) ◽  
pp. R1273-R1284 ◽  
Author(s):  
Jennifer Magnusson ◽  
Kevin J. Cummings
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Arterial Blood Pressure ◽  
Cardiovascular Responses ◽  
Partial Loss ◽  
Rat Pups ◽  
Arterial Blood ◽  
Hypercapnic Hypoxia ◽  
Long Term Facilitation

The role of serotonin (5-HT) neurons in cardiovascular responses to acute intermittent hypoxia (AIH) has not been studied in the neonatal period. We hypothesized that a partial loss of 5-HT neurons would reduce arterial blood pressure (BP) at rest, increase the fall in BP during hypoxia, and reduce the long-term facilitation of breathing (vLTF) and BP following AIH. We exposed 2-wk-old, 5,7-dihydroxytryptamine-treated and controls to AIH (10% O2; n = 13 control, 14 treated), acute intermittent hypercapnia (5% CO2; n = 12 and 11), or acute intermittent hypercapnic hypoxia (AIHH; 10% O2, 5% CO2; n = 15 and 17). We gave five 5-min challenges of AIH and acute intermittent hypercapnia, and twenty ∼20-s challenges of AIHH to mimic sleep apnea. Systolic BP (sBP), diastolic BP, mean arterial pressure, heart rate (HR), ventilation (V̇e), and metabolic rate (V̇o2) were continuously monitored. 5,7-Dihydroxytryptamine induced an ∼35% loss of 5-HT neurons from the medullary raphe. Compared with controls, pups deficient in 5-HT neurons had reduced resting sBP (∼6 mmHg), mean arterial pressure (∼5 mmHg), and HR (56 beats/min), and experienced a reduced drop in BP during hypoxia. AIHH induced vLTF in both groups, reflected in increased V̇e and V̇e/V̇o2, and decreased arterial Pco2. The sBP of pups deficient in 5-HT neurons, but not controls, was increased 1 h following AIHH. Our data suggest that a relatively small loss of 5-HT neurons compromises resting BP and HR, but has no influence on ventilatory plasticity induced by AIHH. AIHH may be useful for reversing cardiorespiratory defects related to partial 5-HT system dysfunction.

scholarly journals Prevalence and Risk Factors of Prolonged QTc Interval among Chinese Patients with Type 2 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Xiang Li ◽  
Hui Ren ◽  
Zhang-rong Xu ◽  
Yan-jun Liu ◽  
Xiao-pin Yang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Waist Circumference ◽  
Qt Interval ◽  
Postprandial Glucose ◽  
Chinese Patients ◽  
Qtc Interval ◽  
Fasting Insulin

Objectives. The aim of this study was to evaluate the prevalence and the risk factors of prolonged QTc interval among Chinese patients with type 2 diabetes.Methods. The retrospective study included 3156 outpatients from the Diabetes Centre, the 306th Hospital of PLA, during the period from September 2003 to June 2010. QT interval was measured manually in the 12-lead conventional electrocardiogram. The QT interval corrected for heart rate (QTc) was calculated using Bazett’s formula. Additional demographic and laboratory data were also collected. Potential risk factors of prolonged QTc interval were assessed using multivariable regression.Results.The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes was 30.1%. Height (OR 0.156, 95% CI 0.032~0.748), waist circumference (OR 1.025, 95% CI 1.010~1.040), diastolic blood pressure (OR 1.016, 95% CI 1.007~1.026), postprandial glucose (OR 1.040, 95% CI 1.022~1.059), fasting insulin (OR 1.014, 95% CI 1.003~1.025), and presence of microalbuminuria (OR 1.266, 95% CI 1.033~1.551) were significant risk factors.Conclusions. The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes is high. Risk factors for prolongation of QTc interval were low height, high waist circumference, increasing diastolic blood pressure levels, high postprandial glucose levels, high fasting insulin levels, and presence of microalbuminuria.

Effects of dietary Ca2+ on erythrocyte Na+-transport systems in spontaneously hypertensive rats

1991 ◽  
Vol 81 (1) ◽  
pp. 107-112 ◽  
Author(s):  
K. Fujito ◽  
M. Yokomatsu ◽  
N. Ishiguro ◽  
H. Numahata ◽  
Y. Tomino ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Transport Systems ◽  
Hypertensive Rats ◽  
Na Transport ◽  
Spontaneously Hypertensive ◽  
Na Pump ◽  
Wistar Kyoto ◽  
Increased Activity ◽  
Regulation Of Blood Pressure

1. The purpose of this study was to determine the effect of dietary Ca2+ intake on blood pressure and erythrocyte Na+ transport in spontaneously hypertensive rats. 2. Spontaneously hypertensive rats and Wistar-Kyoto rats were fed diets with three different Ca2+ contents, 0.1% (low-Ca2+ diet), 0.6% (normal-Ca2+ diet) and 4.0% (high-Ca2+ diet), between 6 and 20 weeks of age. At 20 weeks of age, the levels of erythrocyte Na+ efflux, as well as Na+ and K+ contents in erythrocytes, were measured. 3. On the low-Ca2+ diet, spontaneously hypertensive rats showed an enhancement of hypertension. Conversely, on the high-Ca2+ diet, they showed an attenuation of the increase in blood pressure. Spontaneously hypertensive rats had a lower erythrocyte Na+ content and increased activity of the Na+ pump at higher levels of dietary Ca2+. Passive Na+ permeability and Na+-K+ co-transport were similar in spontaneously hypertensive rats on the low-, normal- and high-Ca2+ diets. There were no significant differences in blood pressure and in Na+ pump activity in WKY on the three different diets. 4. It is concluded that dietary Ca2+ might affect the regulation of blood pressure in spontaneously hypertensive rats by changing the activity of Na+ pump in the cell membrane.

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