Amino acid neurotransmitters in the central control of blood pressure and in experimental hypertension

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.

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Emerging Therapeutics Based on the Amino Acid Neurotransmitter System: An Update on the Pharmaceutical Pipeline for Mood Disorders

Chronic Stress ◽

10.1177/24705470211020446 ◽

2021 ◽

Vol 5 ◽

pp. 247054702110204

Author(s):

Julia Hecking ◽

Pasha A. Davoudian ◽

Samuel T. Wilkinson

Keyword(s):

Amino Acid ◽

Mood Disorders ◽

Phase Iii ◽

Public Health Issue ◽

Complex Nature ◽

Novel Therapies ◽

Amino Acid Neurotransmitters ◽

Neurotransmitter System ◽

Phase Iii Clinical Trials ◽

The World

Mood disorders represent a pressing public health issue and significant source of disability throughout the world. The classical monoamine hypothesis, while useful in developing improved understanding and clinical treatments, has not fully captured the complex nature underlying mood disorders. Despite these shortcomings, the monoamine hypothesis continues to dominate the conceptual framework when approaching mood disorders. However, recent advances in basic and clinical research have led to a greater appreciation for the role that amino acid neurotransmitters play in the pathophysiology of mood disorders and as potential targets for novel therapies. In this article we review progress of compounds that focus on these systems. We cover both glutamate-targeting drugs such as: esketamine, AVP-786, REL-1017, AXS-05, rapastinel (GLYX-13), AV-101, NRX-101; as well as GABA-targeting drugs such as: brexanolone (SAGE-547), ganaxolone, zuranolone (SAGE-217), and PRAX-114. We focus the review on phase-II and phase-III clinical trials and evaluate the extant data and progress of these compounds.

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Levels of monoamine and amino acid neurotransmitters in the developing male mouse hypothalamus and in histotypic hypothalamic cultures

International Journal of Developmental Neuroscience ◽

10.1016/s0736-5748(98)00018-5 ◽

1998 ◽

Vol 16 (5) ◽

pp. 403-412 ◽

Cited By ~ 27

Author(s):

L. Miranda‐contreras ◽

R.V. Mendoza‐Briceño ◽

E.L. Palacios‐Prü

Keyword(s):

Amino Acid ◽

Male Mouse ◽

Amino Acid Neurotransmitters

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Differential Changes in the Content of Amino Acid Neurotransmitters in Discrete Regions of the Rat Brain Prior to the Onset and During the Course of Homocysteine-Induced Seizures

Journal of Neurochemistry ◽

10.1111/j.1471-4159.1986.tb01780.x ◽

1986 ◽

Vol 46 (5) ◽

pp. 1582-1592 ◽

Cited By ~ 38

Author(s):

Ian C. Allen ◽

Angus Grieve ◽

Roger Griffiths

Keyword(s):

Amino Acid ◽

Rat Brain ◽

Amino Acid Neurotransmitters

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Mass Fragmentographic Method for the Determination of Trace Amounts of Putative Amino Acid Neurotransmitters and Related Compounds from Brain Perfusates Collected In Vivo

Journal of Neurochemistry ◽

10.1111/j.1471-4159.1982.tb08650.x ◽

1982 ◽

Vol 38 (2) ◽

pp. 451-456 ◽

Cited By ~ 12

Author(s):

M. Wolfensberger ◽

U. Amsler

Keyword(s):

Amino Acid ◽

Amino Acid Neurotransmitters ◽

Related Compounds

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Renal–adrenal interrelationships in experimental hypertension

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y68-030 ◽

1968 ◽

Vol 46 (2) ◽

pp. 179-188 ◽

Cited By ~ 2

Author(s):

D. Ostrovsky ◽

F. R. Papsin ◽

A. G. Gornall

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Renal Artery ◽

High Blood Pressure ◽

Salt Intake ◽

Renal Tissue ◽

Experimental Hypertension ◽

Normal Blood Pressure ◽

Renal Hypertrophy ◽

High Salt Intake

For several weeks after partial constriction of one renal artery, the fate of this "clipped" kidney seems to exert a determining influence on blood pressure. Rats that remained hypertensive throughout the experiment almost invariably had clipped kidneys averaging 0.16 to 0.22% of body weight. Below 0.1%, this kidney was usually quite atrophic, and its presence was consistent with falling or normal blood pressure. The untouched kidney in such rats was, on the average, heavier in the hypertensive than in the normotensive animals. Since the latter also had less renal tissue on the clipped side, it appears that factors leading to high blood pressure stimulated hypertrophy beyond the level provoked by renoprival factors. In rats on a high salt intake, 5 μg/day of D-aldosterone for 3 months stimulated significant true renal hypertrophy in the absence of a rise in blood pressure. Such hypertrophy was more pronounced in similar rats that had been getting 250 μg DOCA/day for 3 months but were also normotensive. Rats that developed hypertension on this latter regimen had still heavier kidneys. Renal hypertrophy appears to be a prehypertensive phenomenon which persists and can become even more pronounced in hypertension. The highest levels of renal hypertrophy were usually associated with significant adrenal hypertrophy. Endocrine functions may be involved in renal hypertrophy. This concept is discussed in relation to a phospholipid "renin inhibitor" recently isolated from dog and hog kidneys.

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