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 micromol/l) than in controls (7.2+/-0.3 micromol/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.
- MeSH
- aminokyseliny krev MeSH
- chromatografie iontoměničová MeSH
- down regulace MeSH
- homocystein krev MeSH
- hyperhomocysteinemie komplikace metabolismus patofyziologie MeSH
- hypertenze etiologie metabolismus patofyziologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH