Abstract MP09: Effect Of Western Diet On Renal Transcriptome Of Hypertensive Mice Overexpressing Human Angiotensin Receptor Type 1

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Harshada Ketkar ◽  
Samantha Tang ◽  
Sudhir Jain
Keyword(s):  
Blood Pressure ◽  
Renin Angiotensin System ◽  
Renal Tissue ◽  
Western Diet ◽  
Rna Seq ◽  
Angiotensin Ii Receptor ◽  
Regular Diet ◽  
Aged Mice ◽  
Specific Regulation ◽  
Renal Tubular

Over-expression of human angiotensin-II receptor type1 (hAT1R) may cause pathological outcomes due to overactivation of renin-angiotensin system. Transgenic (TG) mice containing Hap-I (hypertensive genotype) of human hAT1R gene are more prone to develop metabolic syndrome disorders as compared to TG mice with Hap-II (normotensive genotype). This gene variant associated risk of hypertension together with Western diet and aging may lead to renal disorders. However, mechanisms underlying this process are not well examined. For this purpose, we studied the renal gene expression alterations in aged TG mice containing either Hap-I or Hap-II of hAT1R gene. Aged mice (20-24 months of age) were maintained on a regular diet or high fat diet with 2% NaCl (Western diet, WD) for 16 weeks. On a regular diet, aged Hap-I mice presented higher (~9 mmHg) systolic blood pressure with respect to age-matched Hap-II animals. Following administration of Western diet, blood pressure increased in both groups of mice, but to a larger extent in Hap-I animals (~15 mmHg in comparison to ~7 mmHg in Hap-II). Aged Hap-I mice on Western diet showed increased renal fibrosis. RNA-seq data from renal tissue of Hap-I aged mice revealed that WD significantly altered the expression of >400 genes (p-adj. <0.05). Bioinformatics analysis (Qiagen IPA software) identified major alterations in main canonical pathways involved in renal function and oxidative damage. These changes in turn resulted in kidney failure, renal tubular injury, and renal proliferation. In addition, post WD treatment, RNA seq. analysis from Hap-I and Hap-II kidneys also reveals haplotype specific regulation of genes associated with blood pressure regulation and kidney disorders. Overall, these results indicate that Western diet promotes hypertension and fibrosis in the kidneys of aged mice. These alterations are paralleled by perturbation of renal transcriptional profile. Overall, these studies will assist in the identification of novel mechanisms and molecules involved in hypertension and associated kidney pathophysiology.

Abstract P479: Pathogenesis And Altered Cardiac Transcriptomic Landscape In Western Diet Treated Aged Mice Overexpressing Human Angiotensin Type 1 Receptor

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Harshada Ketkar ◽  
Samantha Tang ◽  
Sudhir Jain
Keyword(s):  
Blood Pressure ◽  
Control Diet ◽  
Weight Ratio ◽  
Western Diet ◽  
Heart Weight ◽  
Cardiac Complications ◽  
Regular Diet ◽  
Aged Mice ◽  
Increased Risk

Overexpression of human angiotensin II type 1 receptor (hAT1R) may lead to pathophysiological outcomes due to overactivation of the renin angiotensin system. We have shown that transgenic (TG) mice containing Hap-I (hypertensive genotype) of human AT1R gene are more prone to develop metabolic syndrome (MetS) as compared to TG mice with Hap-II (normotensive genotype). The increased risk of MetS, especially in hypertension, compounded by the effects of aging and Western diet (WD), which may lead to cardiac complications. However, the underlying mechanisms are not well examined. For this purpose, we studied the pathophysiological changes and gene expression profile alterations in the heart of aged Hap-I and Hap-II TG mice following exposure to WD. Aged mice (20-24 months of age) were maintained on a regular diet or high fat diet with 2% NaCl (WD) for 16 weeks. On regular diet, aged Hap-I mice presented higher (~9 mmHg) systolic blood pressure with respect to age-matched Hap-II animals. Following administration of WD, blood pressure increased in both groups of mice, but to a larger extent in Hap-I animals (~15 mmHg), in comparison to Hap-II (~7 mmHg). With respect to Hap-II, aged Hap-I mice on regular diet tended to have larger heart weight-to-body weight ratio and higher levels of fibrosis. Western Diet treatment exacerbated these differences. RNA sequencing data from cardiac tissue of WD treated Hap-I aged mice (compared to control diet treated age-matched mice) revealed that WD significantly altered the expression of >500 genes (p-adj. <0.05). Bioinformatics analysis, using Qiagen IPA software, identified major alterations in main canonical pathways involved in cardiac function, inflammation, and oxidative damage. Top hits in the disease and biological function category included arrhythmia, chamber enlargement, and cell death. Importantly, IRF3, IRF7, IFNG and STAT1 were among the top upstream regulators significantly affected by WD. Overall, these results indicate that Western diet promotes hypertension, hypertrophy, and fibrosis in the heart of aged mice. Results from these studies will assist in the identification of novel molecules and mechanisms involved in hypertension and associated cardiac pathophysiology.

Invited Review: Physiological consequences of intermittent hypoxia: systemic blood pressure

2001 ◽  
Vol 90 (4) ◽  
pp. 1600-1605 ◽  
Author(s):  
Eugene C. Fletcher
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Cardiovascular Response ◽  
Acute Hypoxia ◽  
Renin Angiotensin System ◽  
Systemic Blood Pressure ◽  
Angiotensin Ii Receptor ◽  
Obstructive Sleep

One of the major manifestations of obstructive sleep apnea is profound and repeated hypoxia during sleep. Acute hypoxia leads to stimulation of the peripheral chemoreceptors, which in turn increases sympathetic outflow, acutely increasing blood pressure. The chronic effect of these repeated episodic or intermittent periods of hypoxia in humans is difficult to study because chronic cardiovascular changes may take many years to manifest. Rodents have been a tremendous source of information in short- and long-term studies of hypertension and other cardiovascular diseases. Recurrent short cycles of normoxia-hypoxia, when administered to rats for 35 days, allows examination of the chronic cardiovascular response to intermittent hypoxia patterned after the episodic desaturation seen in humans with sleep apnea. The result of this type of intermittent hypoxia in rats is a 10- to 14-mmHg increase in resting (unstimulated) mean blood pressure that lasts for several weeks after cessation of the daily cyclic hypoxia. Carotid body denervation, sympathetic nerve ablation, renal sympathectomy, adrenal medullectomy, and angiotensin II receptor blockade block the blood pressure increase. It appears that adrenergic and renin-angiotensin system overactivity contributes to the early chronic elevated blood pressure in rat intermittent hypoxia and perhaps to human hypertension associated with obstructive sleep apnea.

RENAL TUBULAR RENIN-ANGIOTENSIN SYSTEM AS A MAJOR DETERMINANT OF BLOOD PRESSURE IN LOW RENIN HYPERTENSIVE WOMEN

2004 ◽  
Vol 22 (Suppl. 2) ◽  
pp. S43
Author(s):  
P. Lantelme ◽  
A. Rohrwasser ◽  
M. Vincent ◽  
M. O. Rial ◽  
L. Legedz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renin Angiotensin System ◽  
Major Determinant ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renal Tubular

scholarly journals Safety and Efficacy of Imidapril in the Treatment of Essential Hypertension

2011 ◽  
Vol 3 ◽  
pp. CMT.S7662
Author(s):  
Masashi Okamura ◽  
Susumu Ogawa ◽  
Sadayoshi Ito
Keyword(s):  
Blood Pressure ◽  
Current Knowledge ◽  
Meta Analysis ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Beneficial Effects ◽  
Pressure Independent ◽  
Ras Inhibitors

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are one of the renin angiotensin system (RAS) inhibitors widely used for the treatment of hypertension. Recently, Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) meta-analysis showed that ACEIs had the blood pressure independent beneficial effects on coronary heart events. In this review, we summarized our current knowledge about ACEIs especially imidapril and re-evaluated ACEIs among other RAS inhibitors (RASIs) because ACEIs have wide ranges of beneficial effects in addition to the ACE inhibition which other RASIs do not have such as the up-regulation of bradykinin level, substance P level, the inhibition of matrix metalloproteinase (MMP) activity and stabilization of coronary plaque.

Abstract P242: Role of Human Renal Proximal Tubule Sodium Bicarbonate Cotransporter NBCe2 (SLC4A5) in Salt Sensitivity of Blood Pressure

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
John J Gildea ◽  
Julia M Carlson ◽  
Tran T Hanh ◽  
Dora Bigler Wang ◽  
Peng Xu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sodium Bicarbonate ◽  
Sodium Transport ◽  
Renal Tissue ◽  
Salt Sensitivity ◽  
Bicarbonate Transport ◽  
Nucleotide Polymorphisms ◽  
High Sodium ◽  
Sodium Bicarbonate Cotransporter ◽  
Renal Tubular

The sodium bicarbonate cotransporter NBCe2 (encoded by SLC4A5) partially regulates renal tubular sodium bicarbonate transport. Hypothesis: since SLC4A5 single nucleotide polymorphisms (SNPs, rs10177833 and rs7571842) are associated with salt sensitivity of blood pressure, the gene product, NBCe2, would be involved with the etiology of human salt sensitivity. NBCe2 was localized in freshly fixed renal tissue and in primary and immortalized RPT cell (RPTC) cultures from tissue or isolated from urine. Basal expression of NBCe2 mRNA and protein was not different between RPTCs carrying WT or HV SLC4A5 before or after dopaminergic or angiotensin (II and III) stimulation. However, total transcellular sodium transport, NHE3 protein expression, and Cl-/HCO3- exchanger activity were higher in SLC4A5 HV than WT RPTCs (WT: 8.6±1.2 mM NaCl n=6, 5207.1±386.4 RFU n=36, 0.265±0.006 pH unit/min, n=33 respectively; VS HV: 14.75±0.7 mM NaCl n=4, 6946.2±500.4 RFU n=48, 0.314±0.018 pH unit/min n=35 respectively, p<0.01). Aberrant sodium transport was even more evident after increasing intracellular sodium, which resulted in increased NBCe2 mRNA, NBCe2 protein and bicarbonate transport in HV RPTCs compared to WT (WT 146% ± 24% , 109% ± 4.7%, 89% ± 4.5%, respectively, VS HV 214% ± 23%, 128% ± 5.7%, 141% ± 4.8%, respectively N=8-12, p<0.05). RPTCs carrying HV variants showed increased binding of HNF4A to SLC4A5 DNA, which was blocked by two HNF4A antagonists. Assays in RPTCs isolated from urine showed increased bicarbonate-dependent pH recovery in RPTCs from salt-sensitive subjects who are HV for SLC4A5. NBCe2 under high sodium is hyper-responsive in RPTCs carrying SLC4A5 HV through an aberrant HNF4A-mediated mechanism.

Abstract P165: Exploration of the Mechanism in Which Saccharina Japonica Alleviates an Increase in Blood Pressure in Renovasucular Hypertensive Rats

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Saki Maruyama ◽  
Yukiko Segawa ◽  
Hiroko Hashimoto ◽  
Tomoko Osea ◽  
Nobutaka Kurihara
Keyword(s):  
Blood Pressure ◽  
Mrna Expression ◽  
Control Diet ◽  
Renin Angiotensin System ◽  
Saccharina Japonica ◽  
Left Renal Artery ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Angiotensin Ii Receptor ◽  
Hypertensive Rats

Objective: Saccharina japonica (SJ), one of brown algae, is a common foodstuff in Japan and neighbor countries. Some studies have shown that the intake of SJ decreases blood pressure (BP) in spontaneously hypertensive rats. As well, we previously observed it in 2-kidney, 1-clip renovascular hypertensive (2K1C) rats. However, the mechanism is still unclear. One of possible components of SJ which play an important role in decreasing BP is alginate. Since alginate is richer in the roots than in the blades in SJ, in the present study, we compared the effects in alleviating BP of intake of SJ roots with that of SJ blades in 2K1C rats. We also evaluated angiotensin II receptor type 1 (AT1R) mRNA to investigate the role of renin-angiotensin system in the mechanism. Methods: Male Sprague-Dawley rats (6 wks) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, the rats started receiving a control diet (C) or a diet containing 5.0% (w/w) SJ blades (B), or SJ roots (R) for 6 weeks. The systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the protocol, mean arterial pressure (MAP) was measured in each rat under anesthesia. Then, the aortas were removed for extracting mRNA. AT1R-mRNA expression was evaluated using reverse transcriptase quantitative real-time PCR. Results: SBP was significantly higher in 2K1C-C than SHAM-C through the experiment period (p<0.001). SBP in 2K1C-B and -R was significantly lower than in 2K1C-C (p<0.001). 2K1C-B showed a significant reduction in SBP compared with in 2K1C-R (p<0.05). At the end of the protocol, MAP showed the similar trend to SBP. AT1R mRNA expression was higher in 2K1C than in SHAM, but there were no significant differences among 2K1C-C, -B and -R. Conclusion: Although alginate is richer in the roots than in the blades in SJ, the effects in alleviating BP was higher in the blades than in the roots. Thus, alginate may play no major role in the mechanism. AT1R may not play an important role, neither. Therefore, we need investigate other possible mechanisms.

Role of angiotensin II and catecholamines in blood pressure variability responses to stress in SHR

1996 ◽  
Vol 270 (6) ◽  
pp. R1265-R1272 ◽  
Author(s):  
E. Gaudet ◽  
J. Blanc ◽  
J. L. Elghozi
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Acute Administration ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Air Jet ◽  
Wistar Kyoto

The contribution of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) to blood pressure (BP) and heart rate (HR) variability responses to air-jet stress was assessed in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Activity of the encogenous RAS was suppressed by chronic treatment by a nonpeptide angiotensin II receptor antagonist (Iosartan). The role of alpha 1-adrenoceptor activity was evaluated in rats by acute administration of prazosin. In untreated animals, an air jet induced an increase in systolic BP (SBP; 9 +/- 2 mmHg for WKY and 8 +/- 2 mmHg for SHR) and in HR (56 +/- 19 beats/min for WKY and 76 +/- 8 beats/min for SHR), followed by an increase of the midfrequency (MF; 0.2-0.6 Hz) component of HR in WKY (183%) and by an increase of the MF component of SBP and diastolic BP in SHR (65%). Prazosin prevented BP rises as well as the MF component of BP and HR increases associated with air-jet stress. Chronic suppression of the RAS by losartan did not alter the BP response to the air jet in WKY and slightly reduced it in SHR but abolished all the BP and HR variability changes in both strains. These results indicate that the SNS but not RAS is essential for the BP rise induced by stress and demonstrate that RAS in conjunction with SNS is involved in BP and HR variability changes associated with stress.

Combination ACE Inhibitors and Angiotensin II Receptor Blockers for Hypertension

2003 ◽  
Vol 37 (6) ◽  
pp. 886-889 ◽  
Author(s):  
Patrick M Finnegan ◽  
Brenda L Gleason
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Combination Therapy ◽  
Ace Inhibitors ◽  
Ace Inhibitor ◽  
Renin Angiotensin System ◽  
Reduce Blood Pressure ◽  
Receptor Blocker ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor

OBJECTIVE: To review data concerning combined angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) therapy for hypertension. DATA SOURCES: MEDLINE (1966–April 2003), IPA (1970–April 2003), and EMBASE (1974–April 2003) with search terms of ACE inhibitor, angiotensin receptor blocker, essential hypertension, and combination therapy. DATA SYNTHESIS: ACE inhibitors provide incomplete blockade of the renin–angiotensin system, sometimes leading to loss of blood pressure control. Addition of ARBs may in theory further reduce blood pressure. Studies of combined ACE inhibitor and ARB therapy for managing hypertension were evaluated. CONCLUSIONS: While studies have shown statistically significant blood pressure reductions with ACE/ARB combination therapy, clinical significance is lacking. Further trials are needed before routine use of the combination can be recommended.

The Intrinsic Brain Iso-Renin-Angiotensin System in the Rat: Its Possible Role in Central Mechanisms of Blood Pressure Regulation

1974 ◽  
Vol 48 (s2) ◽  
pp. 265s-268s ◽  
Author(s):  
D. Ganten ◽  
J. S. Hutchinson ◽  
P. Schelling
Keyword(s):  
Blood Pressure ◽  
Cerebrospinal Fluid ◽  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rats ◽  
Renin Angiotensin System ◽  
Angiotensin Ii Receptor ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin

1. Angiotensin is produced by the intrinsic iso-renin-angiotensin system. 2. Angiotensin is secreted into the cerebrospinal fluid of nephrectomized rats. 3. Angiotensin in cerebrospinal fluid elevates systemic blood pressure. 4. Rats with hereditary diabetes insipidus are virtually non-responsive to intraventricular angiotensin. 5. Angiotensin II is elevated in the cerebrospinal fluid of spontaneously hypertensive rats. 6. An intraventricular perfusion of the angiotensin II receptor-blocking agent P 113 decreases blood pressure in spontaneously hypertensive rats.

scholarly journals The Renin-Angiotensin System Modulates Inflammatory Processes in Atherosclerosis: Evidence from Basic Research and Clinical Studies

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
Fabrizio Montecucco ◽  
Aldo Pende ◽  
François Mach
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Basic Research ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renin Inhibitors ◽  
Arterial Blood ◽  
Inflammatory Processes

Recent evidence shows that the renin-angiotensin system is a crucial player in atherosclerotic processes. The regulation of arterial blood pressure was considered from its first description of the main mechanism involved. Vasoconstriction (mediated by angiotensin II) and salt and water retention (mainly due to aldosterone) were classically considered as pivotal proatherosclerotic activities. However, basic research and animal studies strongly support angiotensin II as a proinflammatory mediator, which directly induces atherosclerotic plaque development and heart remodeling. Furthermore, angiotensin II induces proatherosclerotic cytokine and chemokine secretion and increases endothelial dysfunction. Accordingly, the pharmacological inhibition of the renin-angiotensin system improves prognosis of patients with cardiovascular disease even in settings of normal baseline blood pressure. In the present review, we focused on angiotensin-convertingenzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and renin inhibitors to update the direct activities of the renin-angiotensin system in inflammatory processes governing atherosclerosis.

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