Investigations into biochemical changes of genetic hypertensive rats using 1H nuclear magnetic resonance-based metabonomics.
Genetically hypertensive rats provide a simple and accessible model for studying essential hypertension, which is a polygenic, heterogenous and multifactorial disease. Their genetic and metabolic features are of great interest because they may provide insight into the pathophysiological processes underlying essential hypertension. We have investigated the genetic influence on metabolic balance and metabolite excretion patterns in stroke-prone spontaneously hypertensive rats (SHRSP) with established hypertension using 1H NMR-based metabonomics. Urinary metabolite profiles for SHRSP and their age-matched normotensive controls, Wistar Kyoto rats, were acquired using 1H NMR spectroscopy. Principal components analysis was applied to these complex NMR data to facilitate differentiation and determine metabolic differences between urine samples collected from the hypertensive and normotensive rats. Consequently, it was possible to distinguish urine samples between the two strains in the principal components scores plot. The loadings plot showed that taurine, creatine and some unidentified metabolites resonating at around delta 2.48, 3.10 and 3.58 predominantly contributed to the separation. In SHRSP, the urinary levels of taurine and creatine were found to be higher and the intensities of the unknown signals much lower than those in the Wistar Kyoto rats. Although the pathophysiological significance of these components remains to be elucidated, this study suggests that 1H NMR-based metabonomics is a promising approach to provide new information on metabolic changes related to the pathophysiological processes of the genetically hypertensive rats.
Akira
Kazuki
K
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. akira@ps.toyaku.ac.jp
Imachi
Misako
M
Hashimoto
Takao
T
D000818:Animals; D019343:Citric Acid / Q000652:urine; D003401:Creatine / Q000652:urine; D003404:Creatinine / Q000652:urine; D004123:Dimethylamines / Q000652:urine; D004195:Disease Models, Animal; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000652:urine*; D008297:Male; D008744:Methylamines / Q000652:urine; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011522:Protons; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019802:Succinic Acid / Q000652:urine*; D013654:Taurine / Q000652:urine
D004123:Dimethylamines; D007656:Ketoglutaric Acids; D008744:Methylamines; D011522:Protons; D013654:Taurine; D019343:Citric Acid; D019802:Succinic Acid; C034516:dimethylamine; D003404:Creatinine; C005855:trimethyloxamine; D003401:Creatine