摘要
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 compared.Results 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 tissue.Conclusion 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.
目的 阐明苯丙氨酸 (Phe)的代谢动力学异常是否涉及原发性高血压的遗传性发病机制。方法 ①用稳定同位素示踪法比较L (2 ,3D3 )亮氨酸、L (2 ,3D3 )异亮氨酸、L 15N 赖氨酸、L (2 ,3D3 )缬氨酸和L (2 ,3D3 ) phe在双亲均患原发性高血压 (EH)子女 (FH+ )、父母及祖父母有 2人或 2人以上患EH及中风的子女(FS+ )和无家族史的子女 (F )的代谢动力学。②比较自发性高血压大鼠 (SHR)、2肾 1夹高血压大鼠 (2K1C)和正常血压大鼠 (WKY)静注 [3 H phe]后的动力学及组织分布。③比较SHR和WKY的培养血管平滑肌细胞 [3 H phe]的浓度转运过程。结果 ①在FH+ 、FS+ 和SHR均发现 [3 H phe]的代谢动力学异常 ,表现为血浆库表观分布容积增大与细胞间转运速度常数降低倾向。② 2K1C中phe的动力学不变。③在此研究组织中 ,仅高于WKY。SHR及WKY心脏和主动脉phe含量增加。④SHR血管平滑肌细胞L phe的净摄取增加。结论 Phe独特的代谢动力学异常可能涉及EH及中风的遗传性机制。
基金
ThisstudywassupportedbythegrantoftheNationalNaturalSciencesFoundationofChina (No 391735 0
No 39470 62 6)
