Objective To clarify whether the disturbances in metabolic kinetics of the essential aminoacid, phenylalanine (phe), are implicated in the genetic pathogenesis of essential hypertension (EH).Methods 1. L-(2, 3D3)-le...
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Objective To clarify whether the disturbances in metabolic kinetics of the essential aminoacid, phenylalanine (phe), are implicated in the genetic pathogenesis of essential hypertension (EH).Methods 1. L-(2, 3D3)-leucine, L-(2, 3D3)-isoleucine, L-15N-lysine, L-(2, 3D3)-valine and L-(2, 3D3)-phe were used for simultaneously studying comparative metabolic kinetics using stable isotope tracer methods with a GC-MS system. Study groups were the offspring with both parents suffering EH (n=10, FH+), 2 or more than 2 parents and grand-parents with EH and stroke (n=12, FS+) and those without genetic predisposition of EH and stroke (n=12, F) groups. 2. By comparing the radioactive counts of ［3H］-phe, and their weight transformation in blood after 1.5?Ci/kg i.v. administration at defined intervals and in tissues obtained after being sacrified among spontaneously hypertensive rats (SHR), 2 kidney-1 clip hypertensive rats (2K1C) and their normotensive controls (WKY). 3. The time transport and concentration transport of ［3H］-L-phe in cpm between the cultured vascular smooth muscle cell of 5th generation in SHR and WKY were *** A single and unique disturbance of metabolic kinetics in phe were found in FH+, FS+ and SHR. The plasma pool or apparent volume of distribution was enlarged, and the turnover rate constants between plasma and cell tended to show a decrease. The pharmacokinetics of phe in 2K1C was not changed. Only phe content in heart and aorta, the vital organs for predicting BP, were higher in SHR than in WKY tissues studied. Both the time and concentration transport were higher in SHR, e.g., an increment in the net-uptake of L-phe by vascular *** A unique aberrant of metabolic kinetics of phe might be implicated in the inherited pathogenesis of EH and stroke both from clinical and animal studies.
OBJECTIVE: To verify the linkage of the candidate regions identified in a previous study (markers D2S168, D2S151, D2S142 on chromosome 2) with hypertension in Chinese families. METHODS: A genetic linkage study focused...
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OBJECTIVE: To verify the linkage of the candidate regions identified in a previous study (markers D2S168, D2S151, D2S142 on chromosome 2) with hypertension in Chinese families. METHODS: A genetic linkage study focused on chromosome 2 was performed on 240 Chinese families containing 856 patients with essential hypertension. A total of 1080 individuals were genotyped using 9 highly polymorphic microsatellite markers around the candidate regions on chromosome 2 with an average spacing of 5 cM. Non-parametric linkage (NPL), parametric linkage analysis and transmission-disequilibrium test (TDT) with the GENEHUNTER software were used to assess evidence for linkage. RESULTS: Linkage of a region on chromosome 2 around D2S151 and D2S142 with hypertension was confirmed by different statistical methods (NPL, LOD score and TDT). However, the linkage of D2S168 could not be replicated in this extension study. CONCLUSIONS: The data suggest that a region on chromosome 2 at or near the loci of D2S142 and D2S151 may harbor genes responsible for the development of essential hypertension in Chinese.
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