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Hypertension in spontaneously hypertensive rats occurs despite low plasma levels of homocysteine

Journal article
Authors Daniel Kondziella
Henrik Zetterberg
Espen Haugen
Michael Fu
Published in Physiological Research
Volume 57
Issue 3
Pages 487-490
ISSN 0862-8408
Publication year 2008
Published at Wallenberg Laboratory
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 487-490
Language en
Keywords disease, hypertension, homocystein
Subject categories Physiology, Cell and Molecular Biology


Hyperhomocysteinemia has been suggested to induce hypertension due to its role in endothelial dysfunction. However, it remains controversial whether homocysteine and hypertension are truly causally related or merely loosely associated. To test the hypothesis that hyperhomocysteinemia occurs in Spontaneously Hypertensive Rats (SHR) we measured plasma levels of homocysteine in 10 male adult SHR and in 10 normotensive controls using Ion Exchange Chromatography. In addition, plasma concentrations of the 22 most common amino acids were measured to explore the relation of homocysteine with amino acid metabolism. Plasma levels of homocysteine were significantly lower in SHR (4.1 micromol/L +/-0.1) than in controls (7.2 micromol/L +/- 0.3; p<0.00001). The amounts of aminobutyric acid (ABU), alanine, citrulline and valine were decreased as well, whereas we found increased levels of aspartate, glutamate, glutamine, histidine and ornithine. Thus, contrary to our hypothesis, hypertension in SHR occurs despite low plasma levels of homocysteine. We provide a new hypothesis whereby reduced conversion of arginine to citrulline is related to increased ornithine levels, but decreased bioavailability of nitric oxide, resulting in impaired blood vessel relaxation and hypertension. In conclusion, our findings do not necessarily exclude that homocysteine and hypertension might be pathophysiologically connected, but corroborate the notion that hypertension can arise due to mechanisms independent of high homocysteine levels.

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