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±0.1 µmol/l) than in controls (7.2±
0.3 µmol/l) (p<0.00001). The amounts of aminobutyric acid,
alanine, citrulline and valine were also decreased, 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.
Effects of ^|^gamma;-Aminobutyric acid rich Kome Shochu Kasu fermented with Lactobacillus brevis IFO-12005 toward Spontaneously Hypertensive Rats.
