scholarly journals Gene-Level Regulation of Acupuncture Therapy in Spontaneously Hypertensive Rats: A Whole Transcriptome Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Si-Ming Ma ◽  
Jing-Wen Yang ◽  
Jian-Feng Tu ◽  
Na-Na Yang ◽  
Yu-Zheng Du ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Endothelial Function ◽  
Transcriptome Analysis ◽  
Stress Responses ◽  
Spontaneously Hypertensive Rats ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Hypertension is a global health problem. It has been reported that acupuncture at Taichong acupoints (LR3) decreases high blood pressure in spontaneously hypertensive rats. A transcriptome analysis can profile gene expression and its relationship with acupuncture. In this study, rats were treated with 2 weeks of acupuncture followed by regular recording of blood pressure (BP). The mRNA changes in the rostral ventrolateral medulla (RVLM) were evaluated to uncover the genetic mechanisms of acupuncture by using a whole transcript array (Affymetrix Rat Gene 1.0 ST array). BP measurements showed that acupuncture significantly decreased systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR). In the bioinformatics results, 2371 differentially expressed genes (DEGs) were identified, where 83 DEGs were overlapped among Wistar-Kyoto rats (WKYs), spontaneously hypertensive rats (SHRs), and SHRs + acupuncture rats (SHRs+Acu). Gene ontology (GO) and pathway analysis revealed that 279 GO terms and 20 pathways with significant differences were related to oxidative stress, inflammation, and vascular endothelial function. In addition, coexpressed DEGs networks indicated that Cd4 and Il-33 might mediate the cascade of inflammation and oxidative stress responses, which could serve as a potential target of acupuncture treatment. In conclusion, our study demonstrated that acupuncture is a promising therapy for treating hypertension and could regulate multiple biological processes mainly involving oxidative stress, inflammation, and vascular endothelial function.

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

Circulation ◽  
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.

Abstract P150: Sex Difference of Hypertension in Spontaneously Hypertensive Rats: Role of Mitochondrial Oxidative Stress

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Rodrigo O Maranon ◽  
Carolina Dalmasso ◽  
Chetal N Patil ◽  
Jane F Reckelhoff
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Sex Difference ◽  
Spontaneously Hypertensive Rats ◽  
Pressor Response ◽  
Premenopausal Women ◽  
Hypertensive Rats ◽  
Mitochondrial Oxidative Stress ◽  
Spontaneously Hypertensive ◽  
Mitochondrial Superoxide

Men have higher blood pressure (BP) than premenopausal women. Pressor response to oxidative stress may be a major contributor to the sex difference in BP control. Mitochondrial oxidative stress is associated with hypertension; however, whether mitochondrial oxidative stress plays a role in the sex difference in BP is unknown. In the present study, we tested the hypothesis that mitochondrial oxidative stress contributes to the sex difference in BP regulation in spontaneously hypertensive rats (SHR). Young intact (iYMSHR) and castrated males (cYMSHR), and females SHR (YFSHR) (3 mos of age) were implanted with radiotelemeters, and after a 4 day baseline BP, were treated with mitoTempo (0.75 mg/kg/d, sc minipumps), a specific scavenger of mitochondrial superoxide, for 7 days. Following 10 days washout of mito-tempo, rats were treated with Tempol (30 mg/kg/day, po drinking water) for 7 days. iYMSHR have higher blood pressure (by telemetry) than cYMSHR and YFSHR (148±1 mmHg, n=5, vs 132±1 mmHg, n=5, and 139±1 mmHg, n=5; p<0.01, respectively). MitoTempo reduced BP by 6% in iYMSHR (147±1 vs 139±1, n=5; p<0.05) compared to females (3%: 139±1 vs 136±1; n=5; p: NS) and castrated males (4.5%: 132±1 vs 126±1, n=5; p<0.05). After 10 days washout, tempol reduced BP only in iYMSHR (144±1 vs 130±1 mmHg, n=5; p<0.05). Our results suggest that mitochondrial oxidative stress may contribute to BP regulation in male SHR, but has no effect in females. The data also suggest that the presence of testosterone is necessary for the pressor response to oxidative stress in males since Tempol had no effect on BP in castrated males. Further studies examining the effect of steroid hormones and mitochondria in BP regulation are necessary to elucidate the importance of mitochondrial oxidative stress on sex difference of hypertension.

Abstract 261: Chloroquine, an Inhibitor of Endosomal Toll-like Receptors, Improves Blood Pressure and Endothelial Function in Spontaneously Hypertensive Rats

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Cameron G McCarthy ◽  
Camilla F Wenceslau ◽  
Styliani Goulopoulou ◽  
Safia Ogbi ◽  
Takayuki Matsumoto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Function ◽  
Innate Immune System ◽  
Spontaneously Hypertensive Rats ◽  
Innate Immune ◽  
Hypertensive Rats ◽  
Dnase Ii ◽  
Spontaneously Hypertensive ◽  
Immune System Activation ◽  
System Activation

HBPR 2014 Circulating mitochondrial DNA (mtDNA) is elevated in spontaneously hypertensive rats (SHR) and the enzyme responsible for its degradation, DNase II, has decreased activity in SHR tissues. Moreover, a synthetic mtDNA mimetic, specific for TLR 9, causes endothelial dysfunction and elevated blood pressure. Therefore, we sought to inhibit the contribution of mtDNA on innate immune system activation, via inhibition of Toll-like receptor (TLR)9, in SHR. We treated 12-15 week old SHR and Wistar-Kyoto rats (WKY) with chloroquine (CQ; 40mg/kg/day) or vehicle (veh; saline) for 21 days via intraperitoneal injection ( i.p. ). We hypothesized that CQ treatment would improve endothelial function and decrease blood pressure in SHR. Blood pressure was measured pre- and post-treatment via tail cuff and endothelial function was measured via mesenteric resistance artery (MRA) relaxation to acetylcholine (ACh; 10 -9 -10 -5 M) using a wire myograph. Treatment with CQ lowered post-systolic blood pressure in SHR (mmHg, Veh: 201±2 vs. CQ: 185±5 mmHg; p<0.05). No effects of treatment were observed on blood pressure in WKY (p>0.05). CQ abolished the contractile effect to high concentrations of ACh [AUC (%NE pre-contraction), Veh: 160±25 vs. CQ: 277±20; p<0.05] in MRA from SHR. However, no differences were observed in endothelium-independent relaxation to NO-donor sodium nitroprusside [E max (%NE pre-contraction), Veh: 97±12 vs. CQ: 102±26; p<0.05] in MRAs from SHR. Again, no effects of treatment were observed for endothelium-dependent or -independent relaxation in WKY (p>0.05). These data demonstrate the inhibition of endosomal TLRs, including TLR9, improves blood pressure and endothelial function in SHR. Inhibition of TLR9 abrogates the potentially deleterious contribution of increased mtDNA and impaired DNase II activity on innate immune system activation in hypertension.

scholarly journals Effects of Diabetic Hyperglycemia on Central Ang-(1-7)-Mas-R-nNOS Pathways in Spontaneously Hypertensive Rats

2016 ◽  
Vol 40 (5) ◽  
pp. 1186-1197 ◽  
Author(s):  
He Li ◽  
Xian Liu ◽  
Zhongqiao Ren ◽  
Jinxia Gu ◽  
Yingjie Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Cerebral Cortex ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Systemic Injection ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Cerebrovascular Dysfunction ◽  
And Control

Background/Aims: Hypertension is a major cause of stroke, and diabetes can increase incidence of this disease. We determined the role played by central angiotensin-(1-7) [Ang-(1-7)] pathway in modulating spontaneously hypertension with diabetic hyperglycemia. Methods: Western Blot analysis and ELISA were used to determine the protein expression of Ang-(1-7) and its signal pathway Mas-R-nNOS in the cerebral cortex and hippocampus of spontaneously hypertensive rats (SHR) and control animals. In a subset of animals, diabetic hyperglycemia was induced by systemic injection of streptozotocin (STZ). We analyzed a relationship between the levels of central Ang-(1-7) and plasma brain natriuretic peptide (BNP) indicating a risk of ischemic stroke. We further examined the effects of Ang-(1-7) on arterial blood pressure. Results: Our findings demonstrated for the first time that administration of STZ 1) attenuates the levels of Ang-(1-7) in the cerebral cortex and hippocampus, which are closely linked to plasma BNP; and 2) leads to downregulation of central Ang-(1-7)-Mas-R-nNOS pathways. Notably, STZ has greater effects in SHR. Additionally, inhibition of oxidative stress can largely improve downregulation of Ang-(1-7) in diabetic SHR. Moreover, central stimulation of Ang-(1-7) pathway or a blockade of oxidative stress improves systolic blood pressure in diabetic SHR. Conclusions: The Ang-(1-7) signaling pathway is engaged in the adaptive mechanisms associated with diabetic hypertension, suggesting that enhancing Ang-(1-7)-Mas-R-nNOS system is likely to be beneficial in preventing against cardiovascular and cerebrovascular dysfunction and vulnerability related to spontaneously hypertension, particularly to diabetic hypertension.

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