Combined Antihypertensive Effect of Paeoniflorin Enriched Extract and Metoprolol in Spontaneously Hypertensive Rats

BACKGROUND: Hypertension is a great global health challenge and it mostly requires drug combination therapy with the various advantages. Metoprolol (MP) and paeoniflorin are both commonly used for the treatment of hypertension. However, whether they exert synergistic effects on antihypertension or not remains unclear, especially on vascular endothelial function. OBJECTIVE: The purpose of the study is to investigate the advantages of the combined antihypertensive effects of paeoniflorin enriched extract from Radix Paeoniae Alba (RE) and MP in spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: SHR divided into six groups (n = 8 each group), animals in each group were administrated orally with distilled water, MP (6 and 20 mg/kg), RE (30 and 90 mg/kg), and MP (6 mg/kg) combined with RE (30 mg/kg) (MP + RE), respectively, daily for 6 weeks. Blood pressure (BP) and microcirculation were assessed. The organ bath experiment and hematoxylin and eosin staining were, respectively, performed for the functional and pathological vascular function analysis. Immunohistochemistry was applied to detect endothelial nitric oxide synthase (eNOS) expression in aorta, heart, and kidney. Further, high-performance liquid chromatography was employed to quantitatively determine paeoniflorin in RE and MP + RE sample solvent, as well as in plasma of Sprague-Dawley rats (SD) after single-dose administration of them. RESULTS: The results showed that MP + RE significantly reduced BP, increased microcirculation, improved vascular function and pathological changes, and upregulated eNOS expression. MP was also found to increase the blood concentration of paeoniflorin in SD. CONCLUSION: The combination of RE and MP could be used for the treatment of hypertension and could improve microcirculation, upregulate eNOS expression, and mitigate endothelial dysfunction in SHR. SUMMARY: Paeoniflorin enriched extract from Radix Paeoniae Alba and metoprolol exert synergistic antihypertensive effects. Abbreviations used: RE: Paeoniflorin enriched extract from Radix Paeoniae Alba, MP: Metoprolol, MP + RE: MP combined with RE, NC: Normal control, MC: Model control, SHR: Spontaneously hypertensive rats, SD: Sprague-Dawley rats, H and E: Hematoxylin and eosin, BP: Blood pressure, SBP: Systolic blood pressure, DBP: Diastolic blood pressure, MBP: Mean arterial blood pressure, NA: Norepinephrine, ACh: Acetylcholine, SNP: Nitroprusside, NO: Nitric oxide, eNOS: Endothelial nitric oxide synthase, RPA: Radices Paeoniae Alba, IHC: Immunohistochemistry, C(max): Peak concentration, T(max): The time to reach C(max), t(½): Half-life, AUC(0-t): Area under the curve of 0-t time; MRT(0-t): Mean residence of 0-t time; CL: Clearance rate.