Beneficial Effects of Paeoniflorin Enriched Extract on Blood Pressure Variability and Target Organ Damage in Spontaneously Hypertensive Rats

Abstract

Blood pressure variability (BPV) is associated with the development and progression of severe target organ damage (TOD). This study aims to evaluate the protective effect of paeoniflorin enriched extract from Radix Paeoniae Alba (PG) on BPV and TOD in spontaneously hypertensive rats (SHR). All SHR were orally treated with distilled water, metoprolol (MP, 20 mg/kg), and PG (PG-H, 90 mg/kg or PG-L, 30 mg/kg) for a single time or daily for 7 weeks. The 24-hour dynamic blood pressure was monitored and then calculated BPV including long- and short-term systolic blood pressure variability (SBPV), diastolic blood pressure variability (DBPV), mean blood pressure variability (MBPV), and heart rate variability (HRV) as well as the 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP. The protective effects of PG on TOD were observed by histopathologic and biochemical detection. The results indicated that long- and short-term SBPV, DBPV, MBPV, and HRV as well as 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP showed no significant changes after single-dose administration of PG and significantly decreased after administration with PG for 7 weeks. PG could also markedly improve the damage of aorta, heart, kidney, and brain. This study suggested that PG could notably reduce BPV, stabilize blood pressure, and mitigate TOD in SHR.

Figure 1

HPLC-DAD analysis of paeoniflorin. (a) HPLC chromatogram of paeoniflorin enriched extract (PG). (b) HPLC chromatogram of standard substance of paeoniflorin. “Peak A” was identified to be paeoniflorin.

Figure 2

Implantable telemetry technology to monitor dynamic blood pressure in SHR. (a) and (b) The sketch map of intraperitoneal implant site. (c) The transmitting signal device.

Figure 3

Conscious and freely moving animals dynamic blood pressure analysis system to monitor dynamic blood pressure in SHR. (a)–(e) The sketch map of surgical procedure. (f) The transmitting signal device.

Figure 4

Effect on 24-hour total blood pressure of SBP, DBP, and MBP after being intervened by paeoniflorin enriched extract (PG) at one time. (a) The 24-hour dynamic SBP. (b) The 24-hour dynamic DBP. (c) The 24-hour dynamic MBP. (d) Analysis of 24-hour total SBP. (e) Analysis of 24-hour total DBP. (f) Analysis of 24-hour total MBP. SBP: systolic blood pressure; DBP: diastolic blood pressure; MBP: mean blood pressure; MG: model group before treatment; MP: metoprolol positive group; PG-H: PG high dose group (90 mg/kg); PG-L: PG low dose group (30 mg/kg). Data were mean ± SD (n = 3). ^∗P < 0.05 versus MG; ^∗∗P < 0.01 versus MG.

Figure 5

Effect on long- and short-term blood pressure variability of SBPV, DBPV, MBPV, and HRV after being intervened by paeoniflorin enriched extract (PG) at one time. (a) Analysis long- and short-term SBPV. (b) Analysis long- and short-term MBPV. (c) Analysis long- and short-term DBPV. (d) Analysis long- and short-term HRV. SBPV: systolic blood pressure variability; DBPV: diastolic blood pressure variability; MBPV: mean blood pressure variability; HRV: heart rate variability; MG: model group before treatment; MP: metoprolol positive group; PG-H: PG high dose group (90 mg/kg); PG-L: PG low dose group (30 mg/kg). Data were mean ± SD (n = 3). ^∗P < 0.05 versus MG.

Figure 6

Effect on 24-hour total blood pressure of SBP, DBP, and MBP after being intervened by paeoniflorin enriched extract (PG) for seven weeks. (a) The 24-hour dynamic SBP. (b) The 24-hour dynamic DBP. (c) The 24-hour dynamic MBP. (d) Analysis of 24-hour total SBP. (e) Analysis of 24-hour total DBP. (f) Analysis of 24-hour total MBP. SBP: systolic blood pressure; DBP: diastolic blood pressure; MBP: mean blood pressure; MG: model group; MP: metoprolol positive group; PG-H: PG high dose group (90 mg/kg); PG-L: PG low dose group (30 mg/kg). Data were mean ± SD (n = 8). ^∗P < 0.05 versus MG; ^∗∗P < 0.05 versus MG.

Figure 7

Effect on long- and short-term blood pressure variability of SBPV, DBPV, MBPV, and HRV after being intervened by paeoniflorin enriched extract (PG) for seven weeks. (a) Analysis long- and short-term SBPV. (b) Analysis long- and short-term MBPV. (c) Analysis long- and short-term DBPV. (d) Analysis long- and short-term HRV. SBPV: systolic blood pressure variability; DBPV: diastolic blood pressure variability; MBPV: mean blood pressure variability; HRV: heart rate variability; MG: model group; MP: metoprolol positive group; PG-H: PG high dose group (90 mg/kg); PG-L: PG low dose group (30 mg/kg). Data were mean ± SD (n = 8). ^∗P < 0.05 versus MG; ^∗∗P < 0.05 versus MG.

Figure 8

Effect on vascular lesions after being intervened by paeoniflorin enriched extract (PG) for seven weeks. (a) Representative photomicrograph of histopathologic observation for aorta by Masson's trichrome staining (×40). (b) Representative photomicrograph of histopathologic observation for aorta by Masson's trichrome staining (×400). (c) Representative photomicrograph of histopathologic observation for aorta by hematoxylin-and-eosin staining (H&E) (×400). (d) Representative photomicrograph of the eNOS expression in aorta by immunohistochemistry (IHC) (×400). MG: model group; MP: metoprolol positive group; PG-H: PG high dose group (90 mg/kg); PG-L: PG low dose group (30 mg/kg).

Figure 9

Effect on histopathology of heart after being intervened by paeoniflorin enriched extract (PG) for seven weeks. (a) Representative photomicrograph of histopathologic observation for heart by hematoxylin-and-eosin staining (H&E) (×200). (b) Representative photomicrograph of histopathologic observation for heart by Masson's trichrome staining (×40). (c) Representative photomicrograph of the COX-2 expression in heart by immunohistochemistry (IHC) (×400). MG: model group; MP: metoprolol positive group; PG-H: PG high dose group (90 mg/kg); PG-L: PG low dose group (30 mg/kg).

Figure 10

Effect on histopathology of kidney and renal function after being intervened by paeoniflorin enriched extract (PG). (a) Representative photomicrograph of histopathologic observation for glomerulus by hematoxylin-and-eosin staining (H&E) (×400). (b) Representative photomicrograph of histopathologic observation for glomerular afferent arteries by H&E (×400). (c) Representative photomicrograph of histopathologic observation for kidney by Masson's trichrome staining (×40). (d) Representative photomicrograph of the COX-2 expression in kidney by immunohistochemistry (IHC) (×400). (e) The renal function indexes of serum UA, BUN, and Cr. MG: model group; MP: metoprolol positive group; PG-H: PG high dose group (90 mg/kg); PG-L: PG low dose group (30 mg/kg). Data were mean ± SD (n = 8). ^∗∗P < 0.01 versus MG.

Figure 11

Effect on histopathology of brain after being intervened by paeoniflorin enriched extract (PG) for seven weeks. (a) Representative photomicrograph of histopathologic observation for cerebral cortex by hematoxylin-and-eosin staining (H&E) (×200). (b) Representative photomicrograph of histopathologic observation for cerebral cortex blood vessel by H&E (×400). (c) Representative photomicrograph of histopathologic observation for hippocampal CA1 area by H&E (×200). MG: model group; MP: metoprolol positive group; PG-H: PG high dose group (90 mg/kg); PG-L: PG low dose group (30 mg/kg).

Figure 12

Hypertensive target organ damage (TOD) in different tissues.