scholarly journals TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats

2020 ◽  
Author(s):  
Marta Gawrys-Kopczynska ◽  
Marek Konop ◽  
Klaudia Maksymiuk ◽  
Katarzyna Kraszewska ◽  
Ladislav Derzsi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hydrostatic Stress ◽  
Oral Treatment ◽  
Circulatory System ◽  
Correlation Spectroscopy ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Contracting Heart

ABSTRACTBackgroundThere is an ongoing debate whether trimethylamine-oxide (TMAO), a molecule present in seafood and a derivate of microbiota metabolism, is beneficial or harmful for the circulatory system. Interestingly, deep-water animals accumulate TMAO that protects proteins such as lactate dehydrogenase (LDH) against high hydrostatic pressure. We hypothesized that TMAO may benefit the circulatory system by protecting cardiac LDH exposed to hydrostatic stress (HS) produced by contracting heart.Methods and ResultsMale, 6-week-old, Sprague-Dawley (SD, n=40) and Spontaneously-Hypertensive-Heart-Failure (SHHF n=18) rats were divided into either Water or TMAO oral treatment. After 56 weeks, half of Water and TMAO SD rats were given isoprenaline (ISO) to produce catecholamine stress. In vitro, LDH with or without TMAO was exposed to HS (changes in pressure 0-250mmHg x 280min−1) and was evaluated using fluorescence correlation spectroscopy. After 58 weeks of the treatment survival was 100% in SD-Water, SD-TMAO, ISO-TMAO and 90% in ISO-Water. In SHHF-Water survival was 66% vs 100% in SHHF-TMAO. In general, TMAO-treated rats showed higher diuresis and natriuresis. In comparison to SHHF-Water, SHHF-TMAO showed significantly lower diastolic arterial blood pressure, plasma NT-proBNP and expression of angiotensinogen and AT1 receptors in the heart. In separate experiments, intravenous TMAO but not vehicle or urea significantly increased diuresis in SD. In vitro, exposure of LDH to HS with or without TMAO did not affect the protein structure.ConclusionsTMAO reduces mortality in SHHF rats that is associated with diuretic, natriuretic and hypotensive effects. HS produced by the contracting heart is neutral for cardiac LDH structure.

scholarly journals TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Marta Gawrys-Kopczynska ◽  
Marek Konop ◽  
Klaudia Maksymiuk ◽  
Katarzyna Kraszewska ◽  
Ladislav Derzsi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Protein Structure ◽  
Circulatory System ◽  
Correlation Spectroscopy ◽  
Sprague Dawley ◽  
Water Control ◽  
Spontaneously Hypertensive ◽  
Beneficial Effects ◽  
Contracting Heart

Trimethylamine-oxide (TMAO) is present in seafood which is considered to be beneficial for health. Deep-water animals accumulate TMAO to protect proteins, such as lactate dehydrogenase (LDH), against hydrostatic pressure stress (HPS). We hypothesized that TMAO exerts beneficial effects on the circulatory system and protects cardiac LDH exposed to HPS produced by the contracting heart. Male, Sprague-Dawley and Spontaneously-Hypertensive-Heart-Failure (SHHF) rats were treated orally with either water (control) or TMAO. In vitro, LDH with or without TMAO was exposed to HPS and was evaluated using fluorescence correlation spectroscopy. TMAO-treated rats showed higher diuresis and natriuresis, lower arterial pressure and plasma NT-proBNP. Survival in SHHF-control was 66% vs 100% in SHHF-TMAO. In vitro, exposure of LDH to HPS with or without TMAO did not affect protein structure. In conclusion, TMAO reduced mortality in SHHF, which was associated with diuretic, natriuretic and hypotensive effects. HPS and TMAO did not affect LDH protein structure.

scholarly journals Long‐Term Dipeptidyl Peptidase 4 Inhibition Worsens Hypertension and Renal and Cardiac Abnormalities in Obese Spontaneously Hypertensive Heart Failure Rats

2021 ◽  
Author(s):  
Edwin K. Jackson ◽  
Zaichuan Mi ◽  
Delbert G. Gillespie ◽  
Dongmei Cheng ◽  
Stevan P. Tofovic
Keyword(s):  
Heart Failure ◽  
Collagen Iv ◽  
Spontaneously Hypertensive ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitor ◽  
Arterial Blood ◽  
Spontaneously Hypertensive Heart Failure ◽  
Blood Pressures ◽  
Renal Vascular

Background The long‐term effects of dipeptidyl peptidase 4 (DPP4) inhibitors on blood pressure and cardiovascular and renal health remain controversial. Herein, we investigated the extended (>182 days) effects of DPP4 inhibition in a model of spontaneous hypertension, heart failure, diabetes mellitus, obesity and hyperlipidemia. Methods and Results Adult obese spontaneously hypertensive heart failure rats (SHHF) were implanted with radio transmitters for measurement of arterial blood pressures. Two weeks later, SHHF were randomized to receive either a DPP4 inhibitor (sitagliptin, 80 mg/kg per day in drinking water) or placebo. At the end of the radiotelemetry measurements, renal and cardiac function and histology, as well as other relevant biochemical parameters, were assessed. For the first 25 days, mean arterial blood pressures were similar in sitagliptin‐treated versus control SHHF; afterwards, mean arterial blood pressures increased more in sitagliptin‐treated SHHF ( P <0.000001). The time‐averaged mean arterial blood pressures from day 26 through 182 were 7.2 mm Hg higher in sitagliptin‐treated SHHF. Similar changes were observed for systolic (8.6 mm Hg) and diastolic (6.1 mm Hg) blood pressures, and sitagliptin augmented hypertension throughout the light‐dark cycle. Long‐term sitagliptin treatment also increased kidney weights, renal vascular resistances, the excretion of kidney injury molecule‐1 (indicates injury to proximal tubules), renal interstitial fibrosis, glomerulosclerosis, renal vascular hypertrophy, left ventricular dysfunction, right ventricular degeneration, and the ratios of collagen IV/collagen III and collagen IV/laminin in the right ventricle. Conclusions These findings indicate that, in some genetic backgrounds, long‐term DPP4 inhibitor treatment is harmful and identify an animal model to study mechanisms of, and test ways to prevent, DPP4 inhibitor–induced pathological conditions.

Neurons from neonatal hypertensive rats exhibit abnormal membrane properties in vitro

1990 ◽  
Vol 259 (3) ◽  
pp. C389-C396 ◽  
Author(s):  
B. C. Jubelin ◽  
M. S. Kannan
Keyword(s):  
Action Potentials ◽  
Membrane Properties ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Enzymatic Dissociation ◽  
Sd Rats ◽  
High Calcium ◽  
Cervical Ganglia ◽  
Wistar Kyoto

The in vitro membrane properties of neurons from superior cervical ganglia (SCG) of neonatal spontaneously hypertensive (SH), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats were studied with microelectrodes. Neurons were obtained by enzymatic dissociation, plated, irradiated, and studied after 2-5 wk. Most SH neurons showed multiple action potentials in response to an intracellular long-duration depolarizing pulse (multiple firing), whereas most neurons from WKY or SD rats generated only one or two action potentials. Multiple firing was inhibited by low concentrations of cobalt (10(-5) M) but not by tetrodotoxin (TTX) (3 x 10(-6) M). Neither high calcium (5-10 x 10(-3) M) nor the Ca2+(-)channel opener BAY K 8644 (10(-6) M) could induce multiple firing in SD or WKY neurons. However, multiple firing was readily induced by apamin (10(-6) M) or tetraethylammonium chloride (5 x 10(-3) M) (Ca2+(-)activated K+(-)channels blockers), with cobalt and TTX sensitivities similar to native multiple-firing neurons. We conclude that 1) multiple firing is characteristic of neonate SH rats SCG neurons in vitro and depends on regenerative Ca2+ currents; 2) multiple firing in SH neurons results from a lack of activation of a Ca2+(-)activated K+ conductance and not from a lack of internal Ca2+ availability; and 3) multiple firing in SCG neurons mirrors a default in K+ conductance common to all cells in genetically hypertensive individuals.

scholarly journals Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent

2015 ◽  
Vol 309 (2) ◽  
pp. R189-R195 ◽  
Author(s):  
Mercedes Perusquía ◽  
Clayton D. Greenway ◽  
Lisa M. Perkins ◽  
John N. Stallone
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Sprague Dawley ◽  
Peripheral Vasculature ◽  
Similar Reduction ◽  
Arterial Blood ◽  
Sd Rats ◽  
Oxide Synthase

Testosterone (TES) and other androgens exert a direct vasorelaxing action on the vasculature in vitro that is structurally specific and independent of cytosolic androgen receptor (AR). The effects of intravenous androgen infusions on mean arterial blood pressure (BP) and heart rate (HR) were determined in conscious, unrestrained, chronically catheterized, ganglionically blocked (hexamethonium, HEX; 30 mg/kg ip) male Sprague-Dawley (SD) and testicular-feminized male (Tfm; AR-deficient) rats, 16–20 wk of age. BP and HR were recorded at baseline and with increasing doses of androgens (0.375–6.00 μmol·kg−1·min−1 iv; 10 min/dose). Data are expressed as means ± SE ( n = 5–8 rats/group). In SD rats, baseline BP and HR averaged 103 ± 4 mmHg and 353 ± 12 beats/min (bpm). TES produced a dose-dependent reduction in BP to a low of 87 ± 4 mmHg (Δ16%), while HR was unchanged (354 ± 14 bpm). Neither BP (109 ± 3 mmHg) nor HR (395 ± 13 bpm) were altered by vehicle (10% EtOH in 0.9% saline; 0.15 ml·kg−1·min−1, iv). In Tfm, TES produced a similar reduction in BP (99 ± 3 to 86 ± 3 mmHg, Δ13%); HR was unchanged (369 ± 18 bpm). In SD, 5β-dihydrotestosterone (genomically inactive metabolite) produced a greater reduction in BP than TES (102 ± 2 to 79 ± 2 mmHg, Δ23%); HR was unchanged (361 ± 9). A 20-μg iv bolus of sodium nitroprusside in both SD and Tfm rats reduced BP 30–40 mmHg, while HR was unchanged, confirming blockade by HEX. Pretreatment of SD rats with neuronal nitric oxide synthase (nNOS) inhibitor (S-methyl-thiocitrulline, SMTC; 20 μg·kg−1·min−1 × 30 min) abolished the hypotensive effects of TES infusion on BP (104 ± 2 vs. 101 ± 2 mmHg) and HR (326 ± 11 vs. 324 ± 8 bpm). These data suggest the systemic hypotensive effect of TES and other androgens involves a direct vasodilatory action on the peripheral vasculature which, like the effect observed in isolated arteries, is structurally specific and AR-independent, and involves activation of nNOS.

Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat

2001 ◽  
Vol 90 (3) ◽  
pp. 795-803 ◽  
Author(s):  
John Armour ◽  
Karel Tyml ◽  
Darcy Lidington ◽  
John X. Wilson
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Cecal Ligation ◽  
Microvascular Dysfunction ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Plasma Ascorbate ◽  
Ascorbate Concentration

Septic patients have low plasma ascorbate concentrations and compromised microvascular perfusion. The purpose of the present experiments was to determine whether ascorbate improves capillary function in volume-resuscitated sepsis. Cecal ligation and perforation (CLP) was performed on male Sprague-Dawley rats. The concentration of ascorbate in plasma and urine, mean arterial blood pressure, and density of continuously perfused capillaries in the extensor digitorum longus muscle were measured 24 h after surgery. CLP caused a 50% decrease (from 56 ± 4 to 29 ± 2 μM) in plasma ascorbate concentration, 1,000% increase (from 46 ± 13 to 450 ± 93 μM) in urine ascorbate concentration, 20% decrease (from 115 ± 2 to 91 ± 2 mmHg) in mean arterial pressure, and 30% decrease (from 24 ± 1 to 17 ± 1 capillaries/mm) in the density of perfused capillaries, compared with time-matched controls. A bolus of intravenous ascorbate (7.6 mg/100 g body wt) administered immediately after the CLP procedure increased plasma ascorbate concentration and restored both blood pressure and density of perfused capillaries to control levels. In vitro experiments showed that ascorbate (100 μM) inhibited replication of bacteria and prevented hydrogen peroxide injury to cultured microvascular endothelial cells. These results indicate that ascorbate is lost in the urine during sepsis and that a bolus of ascorbate can prevent microvascular dysfunction in the skeletal muscle of septic animals. Our study supports the view that ascorbate may be beneficial for patients with septic syndrome.

Validation of Cardiac Output as Reported by a Permanently Implanted Wireless Sensor

2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Michael Tree ◽  
Jason White ◽  
Prem Midha ◽  
Samantha Kiblinger ◽  
Ajit Yoganathan
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Measurement Accuracy ◽  
Circulatory System ◽  
Left Heart Failure ◽  
Mock Circulatory System ◽  
System A ◽  
Reference Flow ◽  
Relevant Range

The CardioMEMS heart failure (HF) system was tested for cardiac output (CO) measurement accuracy using an in vitro mock circulatory system. A software algorithm calculates CO based on analysis of the pressure waveform as measured from the pulmonary artery, where the CardioMEMS system resides. Calculated CO was compared to that from reference flow probe in the circulatory system model. CO measurements were compared over a clinically relevant range of stroke volumes and heart rates with normal, pulmonary hypertension (PH), decompensated left heart failure (DLHF), and combined DHLF + PH hemodynamic conditions. The CardioMEMS CO exhibited minimal fixed and proportional bias.

Myocardial tumor necrosis factor-α secretion in hypertensive and heart failure-prone rats

1999 ◽  
Vol 277 (2) ◽  
pp. H543-H550 ◽  
Author(s):  
Marina R. Bergman ◽  
Ruey H. Kao ◽  
Sylvia A. McCune ◽  
Bethany J. Holycross
Keyword(s):  
Heart Failure ◽  
Tumor Necrosis Factor ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Tumor Necrosis ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Tnf Α ◽  
Necrosis Factor

Acute increases in blood pressure (BP) increase myocardial tumor necrosis factor (TNF)-α production, but it is not known whether chronic hypertensive stress elevates myocardial TNF-α production, possibly contributing to cardiac remodeling, decreased cardiac function, and faster progression to heart failure. BP, cardiac function, and size were evaluated in normotensive [Sprague-Dawley (SD)], spontaneously hypertensive (SHR), and spontaneously hypertensive heart failure-prone (SHHF) rats at 6, 12, 15, and 18 mo of age and in failing SHHF. Left ventricular tissues were evaluated for secretion of bioactive TNF-α and inhibition of TNF-α secretion by phosphodiesterase inhibitors. All ventricles secreted bioactive and immunoreactive TNF-α, but secretion decreased with age. SHR and SHHF rats secreted more TNF-α than SD rats at 6 mo of age, but only failing SHHF rats secreted significantly more TNF-α at 18 mo. Amrinone inhibited TNF-α secretion in all rats and was less potent but more efficacious than RO-201724 in all strains. TNF-α secretion correlated with BP and left ventricular mass in 6-mo-old rats, but this relationship disappeared with age. Results suggest that hypertension and/or cardiac remodeling is associated with elevated myocardial TNF-α, and, although hypertension, per se, did not maintain elevated cardiac TNF-α levels, SHHF rats increase TNF-α production during the end stages of failure.

Age-dependent augmentation of cardiac endothelial NOS in a genetic rat model of heart failure

1997 ◽  
Vol 273 (3) ◽  
pp. H1223-H1230 ◽  
Author(s):  
F. H. Khadour ◽  
R. H. Kao ◽  
S. Park ◽  
P. W. Armstrong ◽  
B. J. Holycross ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Left Ventricular ◽  
Shr Rats ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Nitrite Level ◽  
Sd Rats ◽  
Enhanced Expression ◽  
Nitrate And Nitrite

Alterations in nitric oxide (NO) biosynthesis in the heart have been implicated in the pathophysiology of heart failure. We compared changes in cardiac nitric oxide synthase (NOS) activity and expression in genetically heart failure-prone (SHHF) rats at 6, 12, and 18 mo of age with those in age-matched spontaneously hypertensive (SHR) and Sprague-Dawley (SD) rats. Systolic blood pressure was significantly higher in SHHF and SHR rats compared with SD rats; however, it declined with age in SHHF rats only. Left ventricular mass increased with age in SHR and SHHF, but not in SD rats. Plasma nitrate and nitrite level was elevated in SHHF and SHR rats at 18 mo only. In left ventricular homogenates from SHHF rats, Ca(2+)-dependent NOS activity increased markedly with age and was accompanied by enhanced expression of endothelial NOS (eNOS). In contrast, SHR rats showed a much smaller increase in Ca(2+)-dependent NOS activity over time without changes in eNOS expression; neither parameter was altered with age in SD rats. Ca(2+)-independent NOS activity was not detected in any heart. This is the first report of a unique alteration in myocardial NOS activity in hypertensive rats genetically prone to heart failure.

Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid ω-hydroxylase activity

2002 ◽  
Vol 283 (3) ◽  
pp. R710-R720 ◽  
Author(s):  
Fengyun Xu ◽  
Wesley O. Straub ◽  
Winnie Pak ◽  
Ping Su ◽  
Kristopher G. Maier ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Vasoconstrictor Response ◽  
Potent Vasoconstrictor ◽  
Acetylenic Fatty Acid ◽  
Regulation Of Blood Pressure

The cytochrome P-450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that is implicated in the regulation of blood pressure. The identification of selective inhibitors of renal 20-HETE formation for use in vivo would facilitate studies to determine the systemic effects of this eicosanoid. We characterized the acetylenic fatty acid sodium 10-undecynyl sulfate (10-SUYS) as a potent and selective mechanism-based inhibitor of renal 20-HETE formation. A single dose of 10-SUYS caused an acute reduction in mean arterial blood pressure in 8-wk-old spontaneously hypertensive rats. The decrease in mean arterial pressure was maximal 6 h after 10-SUYS treatment (17.9 ± 3.2 mmHg; P < 0.05), and blood pressure returned to baseline levels within 24 h after treatment. Treatment with 10-SUYS was associated with a decrease in urinary 20-HETE formation in vivo and attenuation of the vasoconstrictor response of renal interlobar arteries to ANG II in vitro. These results provide further evidence that 20-HETE plays an important role in the regulation of blood pressure in the spontaneously hypertensive rat.

Abstract MP08: Testosterone Contributes To Renal Necrosis In Male Spontaneously Hypertensive Rats (SHR).

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Mahmoud Abdelbary ◽  
Ellen E Gillis ◽  
Jennifer C Sullivan
Keyword(s):  
Blood Pressure ◽  
Flow Cytometric Analysis ◽  
Tubular Epithelial Cell ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Flow Cytometric ◽  
Age Related ◽  
Renal Tubular ◽  
Renal Necrosis

We previously published a sex difference in renal necrosis in SHR with males having a maturation induced increase in renal necrosis that is absent in females. Testosterone is known to drive an increase both in blood pressure (BP) with maturation in male SHR and necrosis of renal tubular epithelial cell in vitro. In the current study we tested the hypothesis that testosterone underlies the maturation induced increase in renal necrosis in male SHR. At 4 weeks of age, male SHR were randomly assigned to either sham or gonadectomy (ORX) groups (n=3). To control for the influence of high BP on renal necrosis, a third group was subjected to a sham surgery and treated with the anti-hypertensive medications hydrochlorothiazide (HCTZ; 55mg/kg/day) and reserpine (Res; 4.5 mg/kg/day) in drinking water starting at 9 weeks of age (n=4) to prevent age-related increases in BP. At 8 weeks of age, telemeters were implanted in all groups followed by a recovery for 1 week before BP was recorded. A separate set of rats were randomly assigned to Sham (n=3), ORX (n=4), or HCTZ/Res (n=4) and subjected to the exact same procedures as the previous set except for telemetry implantation. All rats were euthanized at 13 weeks of age and kidneys were collected for the quantification of renal necrosis using flow cytometric analysis of 7AAD + cells. Data were analyzed using one-way ANOVA and presented as mean ± standard error. BP was significantly lower in ODX and HCTZ/Res treated groups compared to sham (mean arterial blood pressure (mmHg): Sham= 139±2; HCTZ/Res= 117±3; ODX= 126±2; p=0.002; n=3-4). Renal necrosis was also significantly less in ORX rats, but not altered in HCTZ/Res treated groups compared to sham (renal necrosis expressed as % total gated kidney cells: Sham= 6±0.3%; HCTZ/Res=5±0.4%; ODX= 4±0.4%; P=0.003; n=6-7). Testosterone contributes to maturation induced increase in renal necrosis in male SHR.

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