Chronic dietary administration of tryptophan prevents the development of deoxycorticosterone acetate salt induced hypertension in rats

1987 ◽  
Vol 65 (5) ◽  
pp. 753-764 ◽  
Author(s):  
Melvin J. Fregly ◽  
Ora E. Lockley ◽  
Judith van der Voort ◽  
Colin Sumners ◽  
William N. Henley
Keyword(s):  
Cardiac Hypertrophy ◽  
Chronic Treatment ◽  
Specific Binding ◽  
Control Level ◽  
Isotonic Saline ◽  
Acute Administration ◽  
Concomitant Treatment ◽  
Deoxycorticosterone Acetate ◽  
Induced Hypertension ◽  
The Brain

Hypertension developed within 3 to 5 weeks in uninephrectomized rats administered deoxycorticosterone acetate (DOCA) at a dose of 850 μg∙kg−1∙day−1 via Silastic tubes and given isotonic saline to drink. Chronic dietary administration of tryptophan (25 and 50 g/kg of food) to DOCA-treated rats reduced their exaggerated intake of NaCl solution and attenuated the elevation of blood pressure induced by treatment with DOCA alone. Treatment with tryptophan also protected against the reduction in urinary concentrating ability during a 24-h dehydration that is characteristic of DOCA-treated rats. Other tests assessed the responsiveness to the β-adrenergic agonist, isoproterenol. These included measurement of drinking and heart rate following acute administration of isoproterenol. The characteristically depressed drinking and chronotropic responses of DOCA-treated rats to acute administration of isoproterenol were unaffected by tryptophan. Responsiveness to angiotensin II (AII) was also tested by assessment of dipsogenic and metabolic responses to acute administration of AII. The increased drinking and tail skin temperature responses to administration of AII, characteristic of DOCA-treated rats, were reduced in a graded fashion by treatment with graded doses of tryptophan. The specific binding of AII to its receptors in membranes from the diencephalon of the brain was increased by treatment with DOCA but was returned to control level by concomitant treatment with tryptophan. The content of serotonin in the mesencephalon of the brain was not changed significantly by treatment with tryptophan, but the content of 5-hydroxyindole acetic acid in the same region increased significantly, suggesting that turnover of serotonin was increased by chronic treatment with tryptophan. The cardiac hypertrophy characteristic of treatment with DOCA was attenuated significantly by chronic treatment with tryptophan, while the low, resting plasma renin activity of the DOCA-treated group was unchanged. These results suggest that tryptophan provides significant protection against the development of DOCA-induced hypertension, polydipsia, polyuria, and cardiac hypertrophy in rats. It also reduces the hyperresponsiveness to treatment with AII, possibly by decreasing the specific binding of AII to its receptors. It also appears to increase the turnover of serotonin in the brain. Whether either one or all of these is responsible for the antihypertensive effect of tryptophan remains for further study.

A role for thyroid hormones in cold-induced elevation of blood pressure and cardiac hypertrophy

1994 ◽  
Vol 72 (9) ◽  
pp. 1066-1074 ◽  
Author(s):  
Melvin J. Fregly ◽  
Fabian Rossi ◽  
J. Robert Cade
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Thyroid Hormones ◽  
Antithyroid Drug ◽  
Thyroid Stimulating Hormone ◽  
Control Group ◽  
Acute Administration ◽  
Induced Hypertension ◽  
Blood Pressures ◽  
Stimulating Hormone

The systolic blood pressures of two groups of rats that were exposed to cold (5 °C) for 4 weeks were elevated significantly above that of warm-acclimated controls maintained at 24 °C. At this time these groups were given the antithyroid drug aminotriazole in their food at 0.3 g/kg. At the same time, one group was given 15.8 μg thyroxine (T4)/kg body mass per day, while the second received 31.6. The doses were chosen as replacement (15.8 μg/kg) and twice replacement (31.8 μg/kg) for the rats. The results of the study revealed that both groups receiving aminotriazole and T4 had reductions in blood pressure within 1 week of initiation of treatment. Blood pressures reached control level after 5 weeks. Cardiac hypertrophy accompanying cold-induced hypertension was reduced with the lower dose of T4 and prevented with the higher dose. Serum concentrations of T4 and triiodothyronine (T3) in the two treated groups were reduced, while serum thyroid-stimulating hormone concentration and thyroid mass were increased above that of the warm-acclimated control group. This suggests that the rats were hypothyroid relative to the warm-acclimated control group. However, the treated rats grew at the same rate as nontreated, cold-exposed controls and had similar food and water intakes, a similar dipsogenic response to acute administration of isoproterenol, and similar colonic temperatures. These measurements suggest that the rats were not functionally hypothyroid. Nevertheless, the results suggest that a paradigm in which the secretory ability of the thyroid gland is blocked, and T4 is returned at a constant, albeit suboptimal, level, reduced blood pressure and cardiac hypertrophy in cold-exposed rats. Hence, the increased turnover of thyroid hormones that characteristically accompanies exposure to cold plays a role in these changes. These studies also indicate that an increase in the rate of secretion of T4 is not required for survival in cold air.Key words: cold-induced hypertension, thyroxine, triiodothyronine, thyroid-stimulating hormone, aminotriazole, antithyroid drug, blood pressure, cardiac hypertrophy, catecholamines, norepinephrine, epinephrine, dopamine.

Adrenaline-Induced Hypertension in Rats

1981 ◽  
Vol 61 (s7) ◽  
pp. 191s-193s ◽  
Author(s):  
L.-H. Tung ◽  
M. J. Rand ◽  
H. Majewski
Keyword(s):  
Blood Pressure ◽  
Feedback Loop ◽  
Chronic Treatment ◽  
Nerve Terminals ◽  
Concomitant Treatment ◽  
Metoprolol Tartrate ◽  
Osmotic Minipumps ◽  
Pressor Responses ◽  
Induced Hypertension ◽  
Blood Pressures

1. Rats implanted with osmotic minipumps delivering adrenaline intraperitoneally at the rate of 2.9 nmol/h had significantly higher systolic and diastolic pressures from days 2 to 6 after implantation than sham-operated control rats. 2. Concomitant treatment with metoprolol tartrate (2.5 mg/kg, intraperitoneally, twice daily) prevented the elevation in blood pressure induced by adrenaline from osmotic minipumps. Such metoprolol treatment did not affect the blood pressure of control rats. 3. Noradrenaline administered intraperitoneally from osmotic minipumps at the rate of 2.9 nmol/h had no significant effect on blood pressure over a 6-day period of observation. 4. Tachyphylaxis developed to the acute pressor responses to intermittent intravenous infusions of adrenaline in doses of 0.78 μg (4.24 nmol) every 10 min, but after 14 days of such treatment systolic and diastolic blood pressures were significantly greater than in control rats. 5. It is suggested that the increase in blood pressure produced by chronic treatment with adrenaline is due to the uptake and accumulation of adrenaline in noradrenergic nerve terminals, from which it is subsequently released as a cotransmitter that mediates a positive feedback loop on, transmission by acting on prejunctional β-adrenoceptors.

scholarly journals The Brain Renin-Angiotensin System Modulates Angiotensin II–Induced Hypertension and Cardiac Hypertrophy

Hypertension ◽  
2000 ◽  
Vol 35 (1) ◽  
pp. 409-412 ◽  
Author(s):  
Ovidiu Baltatu ◽  
José Antonio Silva ◽  
Detlev Ganten ◽  
Michael Bader
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Induced Hypertension ◽  
The Brain

Benzamil blockade of brain Na+ channels averts Na+-induced hypertension in rats

1998 ◽  
Vol 274 (3) ◽  
pp. R635-R644 ◽  
Author(s):  
Masato Nishimura ◽  
Ken Ohtsuka ◽  
Akira Nanbu ◽  
Hakuo Takahashi ◽  
Manabu Yoshimura
Keyword(s):  
Arterial Pressure ◽  
Urinary Excretion ◽  
Chronic Hypertension ◽  
Hypertensive Rats ◽  
Deoxycorticosterone Acetate ◽  
Intracerebroventricular Infusion ◽  
Acetate Salt ◽  
Induced Hypertension ◽  
Acute Increase ◽  
The Brain

To determine the possible involvement of brain amiloride-sensitive Na+channels in Na+-induced hypertension, we investigated the effects of benzamil hydrochloride, a specific blocker of these Na+channels, on the acute pressor mechanisms of intracerebroventricular infusion of hypertonic NaCl and the continuous pressor mechanisms of Na+-induced chronic hypertension, such as deoxycorticosterone acetate-salt hypertensive or stroke-prone spontaneous hypertensive rats, and of non-Na+-induced hypertension, such as renovascular hypertensive rats. Intracerebroventricular preinjection with benzamil (1 or 10 nmol/kg) abolished the increase in mean arterial pressure, heart rate, abdominal sympathetic discharge, and plasma vasopressin concentration induced by an acute increase in cerebrospinal Na+ concentrations at intracerebroventricular infusion of 1.5 M hypertonic NaCl. Continuous intracerebroventricular infusion of benzamil (1 or 10 nmol ⋅ kg−1 ⋅ day−1) for 7 days attenuated Na+-induced chronic hypertension in both deoxycorticosterone acetate-salt and stroke-prone spontaneous hypertensive rats, accompanied by reduction of urinary excretion of vasopressin and norepinephrine but not in renovascular hypertensive rats. Intravenous infusion of benzamil (10 nmol ⋅ kg−1 ⋅ day−1) for 7 days affected neither arterial pressure nor urinary excretion of vasopressin and norepinephrine in either model of hypertension. Benzamil-blockable brain amiloride-sensitive Na+ channels are expected to function as one of the Na+receptors in the brain and to be involved in the pressor mechanism of Na+-induced hypertension.

scholarly journals Improved in vivo PET imaging of the adenosine A2A receptor in the brain using [18F]FLUDA, a deuterated radiotracer with high metabolic stability

2021 ◽  
Author(s):  
Thu Hang Lai ◽  
Magali Toussaint ◽  
Rodrigo Teodoro ◽  
Sladjana Dukić-Stefanović ◽  
Daniel Gündel ◽  
...  
Keyword(s):  
Specific Binding ◽  
Radiochemical Yield ◽  
Toxicity Study ◽  
In Vivo Evaluation ◽  
One Pot ◽  
Specific Binding Ratio ◽  
Mri Studies ◽  
The Brain

Abstract Purpose The adenosine A2A receptor has emerged as a therapeutic target for multiple diseases, and thus the non-invasive imaging of the expression or occupancy of the A2A receptor has potential to contribute to diagnosis and drug development. We aimed at the development of a metabolically stable A2A receptor radiotracer and report herein the preclinical evaluation of [18F]FLUDA, a deuterated isotopologue of [18F]FESCH. Methods [18F]FLUDA was synthesized by a two-step one-pot approach and evaluated in vitro by autoradiographic studies as well as in vivo by metabolism and dynamic PET/MRI studies in mice and piglets under baseline and blocking conditions. A single-dose toxicity study was performed in rats. Results [18F]FLUDA was obtained with a radiochemical yield of 19% and molar activities of 72–180 GBq/μmol. Autoradiography proved A2A receptor–specific accumulation of [18F]FLUDA in the striatum of a mouse and pig brain. In vivo evaluation in mice revealed improved stability of [18F]FLUDA compared to that of [18F]FESCH, resulting in the absence of brain-penetrant radiometabolites. Furthermore, the radiometabolites detected in piglets are expected to have a low tendency for brain penetration. PET/MRI studies confirmed high specific binding of [18F]FLUDA towards striatal A2A receptor with a maximum specific-to-non-specific binding ratio in mice of 8.3. The toxicity study revealed no adverse effects of FLUDA up to 30 μg/kg, ~ 4000-fold the dose applied in human PET studies using [18F]FLUDA. Conclusions The new radiotracer [18F]FLUDA is suitable to detect the availability of the A2A receptor in the brain with high target specificity. It is regarded ready for human application.

Contribution of specific binding to the central benzodiazepine site to the brain concentrations of two novel benzodiazepine site ligands

2007 ◽  
Vol 28 (6) ◽  
pp. 275-282 ◽  
Author(s):  
Andrew Pike ◽  
Susan M. Cook ◽  
Alan P. Watt ◽  
Paul Scott-Stevens ◽  
Thomas W. Rosahl ◽  
...  
Keyword(s):  
Specific Binding ◽  
The Brain ◽  
Benzodiazepine Site

scholarly journals Genotoxic and oxidative effect of duloxetine on mouse brain and liver tissues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Isela Álvarez-González ◽  
Scarlett Camacho-Cantera ◽  
Patricia Gómez-González ◽  
Michael J. Rendón Barrón ◽  
José A. Morales-González ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Mouse Brain ◽  
Control Level ◽  
Dna Oxidation ◽  
Methyl Methanesulfonate ◽  
Control Group ◽  
Oxidative Potential ◽  
The Brain ◽  
Oxidative Effect

AbstractWe evaluated the duloxetine DNA damaging capacity utilizing the comet assay applied to mouse brain and liver cells, as well as its DNA, lipid, protein, and nitric oxide oxidative potential in the same cells. A kinetic time/dose strategy showed the effect of 2, 20, and 200 mg/kg of the drug administered intraperitoneally once in comparison with a control and a methyl methanesulfonate group. Each parameter was evaluated at 3, 9, 15, and 21 h postadministration in five mice per group, except for the DNA oxidation that was examined only at 9 h postadministration. Results showed a significant DNA damage mainly at 9 h postexposure in both organs. In the brain, with 20 and 200 mg/kg we found 50 and 80% increase over the control group (p ≤ 0.05), in the liver, the increase of 2, 20, and 200 mg/kg of duloxetine was 50, 80, and 135% in comparison with the control level (p ≤ 0.05). DNA, lipid, protein and nitric oxide oxidation increase was also observed in both organs. Our data established the DNA damaging capacity of duloxetine even with a dose from the therapeutic range (2 mg/kg), and suggest that this effect can be related with its oxidative potential.

scholarly journals Potential for imaging the high-affinity state of the 5-HT1B receptor: a comparison of three PET radioligands with differing intrinsic activity

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anton Lindberg ◽  
Ryosuke Arakawa ◽  
Tsuyoshi Nogami ◽  
Sangram Nag ◽  
Magnus Schou ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Specific Binding ◽  
Occipital Cortex ◽  
Intrinsic Activity ◽  
High Affinity ◽  
G Protein Coupled ◽  
Dose Dependent ◽  
The Brain ◽  
Agonist Affinity States ◽  
Different Doses

Abstract Background Over the last decade, a few radioligands have been developed for PET imaging of brain 5-HT1B receptors. The 5-HT1B receptor is a G-protein-coupled receptor (GPCR) that exists in two different agonist affinity states. An agonist ligand is expected to be more sensitive towards competition from another agonist, such as endogenous 5-HT, than an antagonist ligand. It is of interest to know whether the intrinsic activity of a PET radioligand for the 5-HT1B receptor impacts on its ability to detect changes in endogenous synaptic 5-HT density. Three high-affinity 11C-labeled 5-HT1B PET radioligands with differing intrinsic activity were applied to PET measurements in cynomolgus monkey to evaluate their sensitivity to be displaced within the brain by endogenous 5-HT. For these experiments, fenfluramine was pre-administered at two different doses (1.0 and 5.0 mg/kg, i.v.) to induce synaptic 5-HT release. Results A dose-dependent response to fenfluramine was detected for all three radioligands. At the highest dose of fenfluramine (5.0 mg/kg, i.v.), reductions in specific binding in the occipital cortex increased with radioligand agonist efficacy, reaching 61% for [11C]3. The most antagonistic radioligand showed the lowest reduction in specific binding. Conclusions Three 5-HT1B PET radioligands were identified with differing intrinsic activity that could be used in imaging high- and low-affinity states of 5-HT1B receptors using PET. From this limited study, radioligand sensitivity to endogenous 5-HT appears to depend on agonist efficacy. More extensive studies are required to substantiate this suggestion.

Influnce of the beta-adrenergic agonist clenbuterol on plasma catecholamines and lymphocyte beta-receptors

1986 ◽  
Vol 1 (3) ◽  
pp. 234-236
Author(s):  
B. Bondy ◽  
M. Ackenheil ◽  
G. Laakmann ◽  
H.T. Munz
Keyword(s):  
Specific Binding ◽  
Plasma Catecholamines ◽  
Adrenergic System ◽  
Plasma Norepinephrine ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Beta Receptors ◽  
Β Receptor ◽  
Beta Adrenergic Agonist ◽  
The Brain

SummaryThe influence of subchronic application of the β-adrenergic agonist clenbuterol on plasma norepinephrine (NE), epinephrine (E) and β-receptors on lymphocytes was investigated in 8 male, healthy volunteers. Treatment with clenbuterol (0.04 mg/day) for 6 days induced significant reduction of β-receptor specific binding in 7 of the 8 subjects with a mean decrease of 40% (p < 0.01) with no changes in affinity. Concomitantly an increase in the plasma NE concentration was observed (mean 50%, p < 0.01), but no significant overall alteration of E concentration. Our results suggest that β-adrenergic agonists exercise a similar effect on the peripheral adrenergic system and on the adrenergic system in the brain.

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