Differential regulations of blood pressure and perturbed metabolism by total ginsenosides and conventional antihypertensive agents in spontaneously hypertensive rats

Aim: 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. Methods: 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. Results: 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. Conclusion: 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.