China Pharmaceutical University, Nanjing, China.
Acta Pharmacol Sin. 2010 Aug;31(8):930-7. doi: 10.1038/aps.2010.86.
To investigate the regulatory effects of total ginsenosides and the conventional antihypertensive agents (captopril, amlodipine, terazosin and hydrochlorothiazide) on the blood pressure and perturbed metabolism in spontaneously hypertensive rats (SHRs) and to analyze the cause-effect relationships between high blood pressure and the metabolic disorders of hypertension.
SHRs were administrated with total ginsenosides or the antihypertensive agents for eight weeks. Systolic blood pressure (SP) was measured every week and low-molecular-weight compounds in blood plasma were quantitatively analyzed using a nontargeted high-throughput metabolomic tool: gas chromatography/time of flight mass spectrometry (GC/TOFMS) . The metabolic patterns were evaluated using principal components analysis and potential markers of hypertension were identified.
Total ginsenosides and the antihypertensive agents differentially regulated SP and the metabolic pattern in SHRs. Total ginsenosides caused a progressive and prolonged reduction of SP and markedly normalized the perturbed metabolism with 14 of 27 (51.8%) markers of hypertension which were regulated toward normal. Total ginsenosides also reduced free fatty acids' level toward normal levels. In contrast, captopril, amlodipine and terazosin efficiently depressed SP, but had little effect on metabolic perturbation with only 8 (29.6%), 4 (14.8%), and 4 (14.8%) markers, respectively, which were regulated.
The metabolic changes persisted when the blood pressure was lowered by the conventional antihypertensive agents, suggesting that hypertension may not be the cause of the metabolic perturbation in SHRs.
研究总人参皂苷及常规抗高血压药物(卡托普利、氨氯地平、特拉唑嗪和氢氯噻嗪)对自发性高血压大鼠(SHR)血压和代谢紊乱的调节作用,并分析高血压与代谢紊乱之间的因果关系。
给予 SHR 总人参皂苷或抗高血压药物 8 周。每周测量收缩压(SP),并使用非靶向高通量代谢组学工具:气相色谱/飞行时间质谱(GC/TOFMS)定量分析血浆中的低分子量化合物。采用主成分分析评价代谢模式,确定高血压的潜在标志物。
总人参皂苷和抗高血压药物对 SHR 的 SP 和代谢模式有不同的调节作用。总人参皂苷可使 SP 逐渐持续降低,并显著使代谢紊乱正常化,其中 14 个(51.8%)高血压标志物得到调节。总人参皂苷还可使游离脂肪酸水平降至正常水平。相比之下,卡托普利、氨氯地平和特拉唑嗪能有效降低 SP,但对代谢紊乱的影响较小,分别有 8 个(29.6%)、4 个(14.8%)和 4 个(14.8%)标志物得到调节。
当常规抗高血压药物降低血压时,代谢变化仍然存在,这表明高血压可能不是 SHR 代谢紊乱的原因。