Herbal medicine (Oryeongsan) for fluid and sodium balance in renal cortex of spontaneously hypertensive rats

Figures

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  Fig. 1. Effects of chronic treatment with ORS on the daily changes in urine volume (UV, A) and water balance (B), and urinary excretion of Na+ (UNaV, D), and Na+ balance (E), in the normotensive Wistar Kyoto rats (WKY-V) and spontaneously hypertensive rats (SHR-V or SHR-O), respectively, treated with vehicle (V) or ORS (O). Summarized changes in the UV and water balance (C) and UNaV and Na+ balance (F) are also shown. Values are the means ± SEM of 7 days of 1st (I), 2nd (II), and 3rd week (III) of the experiments. Days −3 ∼ −1, control days (C) before administration of ORS are followed by phases (I, II, and III) of vehicle or ORS treatment. Vehicle or ORS (1 ml) was administered orally during the experimental period (days 1 ∼ 24). The dose of ORS was 100 mg/kg/day which is an equivalent amount of a single dose of ORS for an adult subject [4]. Numerals above or below the markings; 1, P < 0.05; 2, P < 0.01; 3, P < 0.001 vs corresponding controls, WKY-V or SHR-V. Numerals in red are significance test between the SHR-ORS and SHR-V groups and those in black are the tests between the SHR-V and WKY-V. Number of experiments for the comparisons between the groups in (A), (B), (D) and (E); WKY-V,…

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  Fig. 2. Summarized effects of chronic treatment with ORS on the (A) urinary volume (UV, a), urinary excretion of Na+ (UNaV, b), K+ (UKV, c), and Cl− (UClV, d) and (B) clearance for creatinine (CCr, glomerular filtration rate, GFR, a), clearance for Na+ (CNa, b), and percent changes in the fractional excretion of Na+ (FENa%, percent changes in CNa/GFR, c) during the last 7 (A) or 3 (B) days (of the third week) of ORS treatment. V, vehicle-treated; O, ORS-treated. *P < 0.05, ***P < 0.001 vs. WKY-V.; ##P < 0.01, ###P < 0.001 vs. SHR-V; Number of experiments: n = 7 days (last 3rd week) for WKY-V, SHR-V, and SHR-ORS groups for 2A; n = 3 days (last 3 days) for each group of 2B For the calculation of the levels of the GFR and CNa of the last 3 days, the last day plasma samples were used.

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  Fig. 3. Effects of chronic treatment with ORS on the impaired vasodilation (A) and gene expression of components of the renin-angiotensin system (B) of the aorta from SHR. A. Acetylcholine induced vasodilation was significantly suppressed and shifted right-upward in the aorta from SHR-V group (S-V) compared to that of normotensive WKY-V group (W-V). Chronic treatment with ORS reversed the suppression and shifted the response toward left-downward in the SHR-ORS group (S-O) compared to the SHR-V group. Number of experiments; WKY-V, n = 4, SHR-V, n = 4, SHR-ORS, n = 4. ***P < 0.001 vs. WKY-v; #P < 0.05, ##P < 0.01, ###P < 0.001 vs. SHR-V. B. Impaired vasodilation of the aorta was accompanied by combined increase in the AT1R gene expression and decrease in the AT2R expression in the aorta from SHR-V. Chronic treatment with ORS reversed abundance of the gene expression in the aorta from SHR-ORS. **P < 0.01 vs. WKY-V; ##P < 0.01 vs. SHR-V.

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  Fig. 4. SBP significantly increased as a time function in SHR-V group compared to WKY-V. Chronic treatment with ORS (100 mg/kg/day, orally) significantly decreased SBP in SHR-ORS group compared to SHR-V. After 1 week of treatment with ORS the decrease was significant and further decreased up to 3rd week of the treatment in the SHR-ORS group. SBP of the normotensive WKY-V group slightly but significantly increased. Number of experiments; WKY-V, n = 4: SHR-V, n = 6: SHR-ORS, n = 5. ***P < 0.001 vs. WKY-V; ###P < 0.001 vs. SHR-V. $P < 0.05 vs. 7th week. Weeks 7-11 are weeks after birth of rats used.

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  Fig. 5. Effects of chronic treatment with ORS on the gene expression of the components of the RAS, NPS and NHE3 in the cortex of the right kidney from SHR and WKY. Assay was performed in triplicate. Number of experiments; n = 6 for W (WKY)-V, n = 7 for both S (SHR)-V and S (SHR)-O (ORS). There are two open red bars in succession with different meanings in S-V group. First one is normalized compared to the values of the normotensive W-V group, and the other is normalized compared to hypertensive group treated with vehicle. **P < 0.01, ***P < 0.001 vs. W-V; #P < 0.05, ##P < 0.01, ###P < 0.001 vs. SHR-V.

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  Fig. 6. Antihypertensive effects of ORS through modulation of the renal cortical function and vasodilation via the RAS, NPS and NHE3 signaling in SHR. Chronic treatment with ORS decreased Na+ and water retention through inhibition of the NHE3 expression along with suppression of the ACE-AT1 receptor expression and accentuation of the AT2 receptor, Mas receptor, and modulation of the NPS in the renal cortex (proximal tubule) of the SHR. In addition, ORS treatment ameliorated defective vasodilation through modulation of the AT1 receptor and AT2 receptor in the vascular bed. These findings provide experimental evidence showing that chronic treatment with ORS decreases high blood pressure through improving body fluid volume and pressure homeostasis and partly vasodilation in the SHR. NHE3, Na+-H+ exchanger 3; AT1R, angiotensin II type 1 receptor; AT2R, angiotensin II type 2 receptor; ANP, atrial natriuretic peptide; NPR-C, natriuretic peptide receptor C; GFR, glomerular filtration rate; UNaV, urinary excretion of Na+; SBP, systolic blood pressure; ORS, Oryeongsan.