scholarly journals Combination of Hypertension and High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 Pathways

2017 ◽  
Author(s):  
Yuan Yuan ◽  
Hisao Naito ◽  
Kazuya Kitamori ◽  
Tamie Nakajima
Keyword(s):  
Transforming Growth Factor ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
High Fat ◽  
Hypertensive Rats ◽  
Nf Kappa B ◽  
Spontaneously Hypertensive ◽  
Hepatic Expression ◽  
Mitogen Activated Protein ◽  
Wistar Kyoto

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

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

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3893-3900 ◽  
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.

scholarly journals Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Omotayo O. Erejuwa ◽  
Siti A. Sulaiman ◽  
Mohd S. Ab Wahab ◽  
Kuttulebbai N. S. Sirajudeen ◽  
Salzihan Salleh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Mrna Expression ◽  
Spontaneously Hypertensive Rats ◽  
Antihypertensive Effect ◽  
Related Factor ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Elevated Systolic Blood Pressure ◽  
Wistar Kyoto

Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.

Excess oxygen delivery during muscle contractions in spontaneously hypertensive rats

1995 ◽  
Vol 78 (1) ◽  
pp. 101-111 ◽  
Author(s):  
J. M. Lash ◽  
H. G. Bohlen
Keyword(s):  
Blood Flow ◽  
Oxygen Saturation ◽  
Oxygen Delivery ◽  
Spontaneously Hypertensive Rats ◽  
Muscle Contractions ◽  
Hypertensive Rats ◽  
Hemoglobin Oxygen Saturation ◽  
Spontaneously Hypertensive ◽  
Tissue Po2 ◽  
Wistar Kyoto

These experiments determined whether a deficit in oxygen supply relative to demand could account for the sustained decrease in tissue PO2 observed during contractions of the spinotrapezius muscle in spontaneously hypertensive rats (SHR). Relative changes in blood flow were determined from measurements of vessel diameter and red blood cell velocity. Venular hemoglobin oxygen saturation measurements were performed by using in vivo spectrophotometric techniques. The relative dilation [times control (xCT)] of arteriolar vessels during contractions was as large or greater in SHR than in normotensive rats (Wistar-Kyoto), as were the increases in blood flow (2 Hz, 3.50 +/- 0.69 vs. 3.00 +/- 1.05 xCT; 4 Hz, 10.20 +/- 3.06 vs. 9.00 +/- 1.48 xCT; 8 Hz, 16.40 +/- 3.95 vs. 10.70 +/- 2.48 xCT). Venular hemoglobin oxygen saturation was lower in the resting muscle of SHR than of Wistar-Kyoto rats (31.0 +/= 3.0 vs. 43.0 +/- 1.9%) but was higher in SHR after 4- and 8-Hz contractions (4 Hz, 52.0 +/- 4.8 vs. 43.0 +/- 3.6%; 8 Hz, 51.0 +/- 4.6 vs. 41.0 +/- 3.6%). Therefore, an excess in oxygen delivery occurs relative to oxygen use during muscle contractions in SHR. The previous and current results can be reconciled by considering the possibility that oxygen exchange is limited in SHR by a decrease in anatomic or perfused capillary density, arteriovenular shunting of blood, or decreased transit time of red blood cells through exchange vessels.

scholarly journals Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury

2021 ◽  
Vol 22 (3) ◽  
pp. 1382
Author(s):  
Jelena Nesovic Ostojic ◽  
Milan Ivanov ◽  
Nevena Mihailovic-Stanojevic ◽  
Danijela Karanovic ◽  
Sanjin Kovacevic ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protein Expression ◽  
Hyperbaric Oxygen ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Kidney Injury ◽  
Heme Oxygenase 1 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.

scholarly journals Aging Additively Influences Insulin- and Insulin-Like Growth Factor-1-Mediated Endothelial Dysfunction and Antioxidant Deficiency in Spontaneously Hypertensive Rats

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 676
Author(s):  
Kunanya Masodsai ◽  
Yi-Yuan Lin ◽  
Sih-Yin Lin ◽  
Chia-Ting Su ◽  
Shin-Da Lee ◽  
...  
Keyword(s):  
Growth Factor ◽  
Endothelial Dysfunction ◽  
Spontaneously Hypertensive Rats ◽  
No Production ◽  
Organ Bath ◽  
Insulin Like Growth Factor ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Nos Inhibitors ◽  
Wistar Kyoto

This study aimed to investigate the aging-related endothelial dysfunction mediated by insulin and insulin-like growth factor-1 (IGF-1) and antioxidant deficiency in hypertension. Male spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar–Kyoto rats (WKYs) were randomly divided into 24-week-old (younger) and 48-week-old (older) groups, respectively. The endothelial function was evaluated by the insulin- and IGF-1-mediated vasorelaxation of aortic rings via the organ bath system. Serum levels of nitric oxide (NO), malondialdehyde (MDA), catalase, and total antioxidant capacity (TAC) were examined. The insulin- and IGF-1-mediated vasorelaxation was significantly impaired in both 24- and 48-week-old SHRs compared with age-matched WKYs and was significantly worse in the 48-week-old SHR than the 24-week-old SHR. After pretreatments of phosphoinositide 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the insulin- and IGF-1-mediated vasorelaxation became similar among four groups. The serum level of MDA was significantly increased, while the NO, catalase, and TAC were significantly reduced in the 48-week-old SHR compared with the 24-week-old SHR. This study demonstrated that the process of aging additively affected insulin- and IGF-1-mediated endothelial dysfunction in SHRs, which could be partly attributed to the reduced NO production and antioxidant deficiency.

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