Mixed Aqueous Extract of Salvia Miltiorrhiza Reduces Blood Pressure through Inhibition of Vascular Remodelling and Oxidative Stress in Spontaneously Hypertensive Rats

Background/Aims: Salvia miltiorrhiza (SM) contains four major aqueous active ingredients, which have been isolated, purified and identified as danshensu (DSS), salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and protocatechuic aldehyde (PAL), totally abbreviated as SABP. Although SM is often used to treat various cardiovascular diseases in traditional Chinese medicine, the efficacy and function of optimal compatibility ratio of SM's active ingredients (SABP) in the prevention and treatment of cardiovascular diseases remain uncertain. This study investigated antihypertensive effect and underlying mechanisms of SABP vs. SM lyophilized powder (SMLP) in spontaneously hypertensive rats (SHR) and to establish the ratio of the optimal compatibility of DSS, Sal-A, Sal-B and PAL in improving cardiovascular functions. Methods: The SHRs were treated with either SABP or SMLP and their systolic blood pressures (SBP) were monitored. The isolated thoracic aorta of SHRs was segregated for immunohistochemistry, Hematoxylin-Eosin stain and mRNA and protein expression of NOX4, TGF-β1, Col-I, ET-1, α-SMA and Smad7. Moreover, the adventitial fibroblasts (AFs) were isolated and cultured from SD rats' aorta and the reactive oxygen species (ROS) production was determined after SABP or SMLP treatment. Results: SABP, but not SMLP, significantly reduced SBP, which were accompanied by the inhibited morphological changes in the thoracic aorta and the reduced mRNA and protein expression of NOX4, TGF-β1, Col-I, ET-1 and α-SMA, but the increased Smad 7 expression in SHRs. Moreover, SABP also resulted in a decreased ROS production in AFs of SD rats. Conclusions: These results indicate that SABP, but not SMLP, treatment potently inhibits hypertension through improvements of vascular remodeling and oxidative stress. The present study provides new evidence that the efficacy and function from optimal compatibility ratio of SM active ingredients is much better than its lyophilized powder, which represents a strategy to develop SM's new beneficial effect in improving cardiovascular functions.

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Induction of heme oxygenase-1 and stimulation of cGMP production by hemin in aortic tissues from hypertensive rats

Blood ◽

10.1182/blood-2002-08-2608 ◽

2003 ◽

Vol 101 (10) ◽

pp. 3893-3900 ◽

Cited By ~ 60

Author(s):

Joseph Fomusi Ndisang ◽

Lingyun Wu ◽

Weimin Zhao ◽

Rui Wang

Keyword(s):

Heme Oxygenase ◽

Macrophage Infiltration ◽

Heme Oxygenase 1 ◽

Zinc Protoporphyrin ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Vascular Tissues ◽

Wistar Kyoto ◽

And Function ◽

Cardiovascular Functions

Abstract Heme oxygenase (HO) and carbon monoxide (CO) have been implicated in the modulation of various cardiovascular functions including blood pressure (BP) regulation. Up-regulating the HO/CO system lowers BP in young (8-week-old) but not in adult (20-week-old) spontaneously hypertensive rats (SHRs). The mechanisms for this selective effect are largely unknown. We investigated the effects of HO-1 inducer, hemin, on the HO/CO-soluble gyanylyl cyclase (sGC)/cGMP system in the aorta of prehypertensive (4-week-old) young and adult SHRs as well as age-matched Wistar-Kyoto rats (WKYs). Reduced expressions of HO-1, HO-2, and sGC proteins associated with depressed HO activity and cGMP levels were detected in young SHRs. These deficiencies were significantly reversed by hemin treatment. Macrophage infiltration of vascular tissues was more significant in adult SHRs than adult WKYs, but invisible in young SHRs and WKYs. Hemin treatment did not alter macrophage infiltration of vascular tissues in young SHRs. The same hemin administration resulted in a significant decrease in BP (from 148.6 ± 3.2 to 125.8 ± 2.6 mmHg, P < .01) in young SHRs, but not in prehypertensive or adult SHRs or WKYs of all ages. The HO inhibitor zinc protoporphyrin abrogated the hemin effect in young SHRs. Aortic tissues became desensitized to YC-1, an activator sGC, in adult SHRs. Thus, in young SHRs the expression and function of the HO/CO-sGC/cGMP system were suppressed, constituting a pathogenic mechanism for the development of hypertension. In adult SHRs, the HO/CO-sGC/cGMP system appeared normal, but desensitization of the sGC/cGMP pathway caused hypertension to prevail.

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1638: Erectile Dysfunction and Oxidative Stress-Media Ted Cavernosal Cell Death in Spontaneously Hypertensive Rats

The Journal of Urology ◽

10.1016/s0022-5347(18)38846-3 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 433-433

Author(s):

Steven Kuntz ◽

Steven White ◽

Michael Alba ◽

Mahadevan Rajasekaran

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Erectile Dysfunction ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

And Oxidative Stress

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MST3 is involved in ENaC-mediated hypertension

AJP Renal Physiology ◽

10.1152/ajprenal.00455.2018 ◽

2019 ◽

Vol 317 (1) ◽

pp. F30-F42

Author(s):

Te-Jung Lu ◽

Wei-Chih Kan ◽

Sung-Sen Yang ◽

Si-Tse Jiang ◽

Sheng-Nan Wu ◽

...

Keyword(s):

Kidney Cells ◽

Hypertensive Rats ◽

Madin Darby Canine Kidney ◽

Spontaneously Hypertensive ◽

Hypomorphic Mutation ◽

And Oxidative Stress ◽

Darby Canine Kidney ◽

Canine Kidney

Liddle syndrome is an inherited form of human hypertension caused by increasing epithelial Na+ channel (ENaC) expression. Increased Na+ retention through ENaC with subsequent volume expansion causes hypertension. In addition to ENaC, the Na+-K+-Cl− cotransporter (NKCC) and Na+-Cl− symporter (NCC) are responsible for Na+ reabsorption in the kidneys. Several Na+ transporters are evolutionarily regulated by the Ste20 kinase family. Ste20-related proline/alanine-rich kinase and oxidative stress-responsive kinase-1 phosphorylate downstream NKCC2 and NCC to maintain Na+ and blood pressure (BP) homeostasis. Mammalian Ste20 kinase 3 (MST3) is another member of the Ste20 family. We previously reported that reduced MST3 levels were found in the kidneys in spontaneously hypertensive rats and that MST3 was involved in Na+ regulation. To determine whether MST3 is involved in BP stability through Na+ regulation, we generated a MST3 hypomorphic mutation and designated MST3+/− and MST3−/− mice to examine BP and serum Na+ and K+ concentrations. MST3−/− mice exhibited hypernatremia, hypokalemia, and hypertension. The increased ENaC in the kidney played roles in hypernatremia. The reabsorption of more Na+ promoted more K+ secretion in the kidney and caused hypokalemia. The hypernatremia and hypokalemia in MST3−/− mice were significantly reversed by the ENaC inhibitor amiloride, indicating that MST3−/− mice reabsorbed more Na+ through ENaC. Furthermore, Madin-Darby canine kidney cells stably expressing kinase-dead MST3 displayed elevated ENaC currents. Both the in vivo and in vitro results indicated that MST3 maintained Na+ homeostasis through ENaC regulation. We are the first to report that MST3 maintains BP stability through ENaC regulation.

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Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats

Cardiovascular Diabetology ◽

10.1186/1475-2840-12-152 ◽

2013 ◽

Vol 12 (1) ◽

pp. 152 ◽

Cited By ~ 26

Author(s):

Camila Rosa ◽

Natasha Xavier ◽

Dijon Henrique Campos ◽

Ana Angélica Fernandes ◽

Marcelo Diarcadia Cezar ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Cardiac Remodeling ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

And Oxidative Stress

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The Enhancement of Cx45 Expression and Function in Renal Interlobar Artery of Spontaneously Hypertensive Rats at Different Age

Kidney & Blood Pressure Research ◽

10.1159/000368482 ◽

2015 ◽

Vol 40 (1) ◽

pp. 52-65 ◽

Cited By ~ 11

Author(s):

Li Li ◽

Wen Zhang ◽

Wen Yan Shi ◽

Ke-Tao Ma ◽

Lei Zhao ◽

...

Keyword(s):

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

And Function

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Abstract 1378: NFkb Blockade Attenuate Cytokines And Oxidative Stress In The Paraventricular Nucleus And Decreases Neurohumoral Excitation In Spontaneously Hypertensive Rats

Circulation ◽

10.1161/circ.116.suppl_16.ii_283-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Nithya Mariappan ◽

Carrie Elks ◽

Masudul Haque ◽

Philip J Ebnezer ◽

Elizabeth McIIwain ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Paraventricular Nucleus ◽

Spontaneously Hypertensive Rats ◽

Left Ventricular ◽

Oxidative Stress Markers ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Stress Markers ◽

And Oxidative Stress

The transcriptional factor, nuclear factor kappa B (NFkB) plays an important role in the regulation of cytokines. Among the cytokines, tumor necrosis factor-alpha (TNF) plays an important role in cardiovascular pathophysiology. This study was done to determine whether TNF-α blockade with etanercept (ETN) or NFkB blockade with dithiol pyrolidine thiocarbamate (PDTC) attenuate oxidative stress in the paraventricular nucleus (PVN) and contribute to neurohumoral excitation in spontaneously hypertensive rats. Method: Male 20 week old SHR rats were treated with ETN (1 mg/kg BW, sc) or PDTC (100mg/kg BW, ip) for 5 week period. Left ventricular function was measured at baseline (20 weeks) and at 25 weeks using echocardiography. Blood pressure was measured at weekly intervals throughout the study. At the end of the protocol rats were sacrificed the PVN was microdissected for the measurement of cytokines, oxidative stress markers using real time PCR (fold increase compared to WKY controls) and by immunohistochemistry. Superoxide, total reactive oxygen species and peroxynitrite were measured in the PVN and LV using electron paramagnetic resonance. Plasma norepinephrine and epinephrine an indicator of neurohumoral excitation was measured using HPLC-EC. Results: PVN data are tabulated. SHR animals had increased expression of protein and mRNA for cytokines and oxidative stress markers in the PVN and LV with increased MAP and cardiac hypertrophy when compared to WKY rats. Treatment with ETN and PDTC attenuated these increases with PDTC showing marked effect than ETN on hypertrophy and blood pressure responses. Conclusion: These findings suggest that cytokine activation in the PVN contributes to increased oxidative stress and neurohumoral excitation in hypertension.

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