scholarly journals Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats

2020 ◽  
Vol 21 (12) ◽  
pp. 4289
Author(s):  
Carla L. Busceti ◽  
Maria Cotugno ◽  
Franca Bianchi ◽  
Maurizio Forte ◽  
Rosita Stanzione ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Lentiviral Vector ◽  
Uncoupling Protein ◽  
Organ Damage ◽  
Kidney Damage ◽  
Uncoupling Protein 2 ◽  
Mrna Levels ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Protein Levels

The downregulation of uncoupling protein-2 (UCP2) is associated with increased brain and kidney injury in stroke-prone spontaneously hypertensive rats (SHRSP) fed with a Japanese style hypersodic diet (JD). Systemic overexpression of UCP2 reduces organ damage in JD-fed SHRSP. We examined the effect of brain-specific UCP2 overexpression on blood pressure (BP), stroke occurrence and kidney damage in JD-fed SHRSP. Rats received a single i.c.v. injection of a lentiviral vector encoding UCP2 (LV-UCP2), or an empty vector. The brain delivery of LV-UCP2 significantly delayed the occurrence of stroke and kidney damage. The large reduction of proteinuria observed after LV-UCP2 injection was unexpected, because BP levels were unchanged. At the time of stroke, rats treated with LV-UCP2 still showed a large UCP2 upregulation in the striatum, associated with increases in OPA1 and FIS1 protein levels, and reductions in PGC1-α, SOD2, TNFα mRNA levels and NRF2 protein levels. This suggested UCP2 overexpression enhanced mitochondrial fusion and fission and reduced oxidative damage and inflammation in the striatum of JD-fed SHRSP rats. Our data suggest the existence of central mechanisms that may protect against hypertension-induced organ damage independently of BP, and strengthen the suitability of strategies aimed at enhancing UCP2 expression for the treatment of hypertensive damage.

Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated by losartan but not by amlodipine

2006 ◽  
Vol 290 (6) ◽  
pp. R1616-R1625 ◽  
Author(s):  
Elena M. V. de Cavanagh ◽  
Jorge E. Toblli ◽  
León Ferder ◽  
Bárbara Piotrkowski ◽  
Inés Stella ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Superoxide Dismutase ◽  
Mitochondrial Dysfunction ◽  
Spontaneously Hypertensive Rats ◽  
Manganese Superoxide Dismutase ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Manganese Superoxide

Mitochondrial dysfunction is associated with cardiovascular damage; however, data on a possible association with kidney damage are scarce. Here, we aimed at investigating whether 1) kidney impairment is related to mitochondrial dysfunction; and 2) ANG II blockade, compared with Ca2+ channel blockade, can reverse potential mitochondrial changes in hypertension. Eight-week-old male spontaneously hypertensive rats (SHR) received water containing losartan (40 mg·kg−1·day−1, SHR+Los), amlodipine (3 mg·kg−1·day−1, SHR+Amlo), or no additions (SHR) for 6 mo. Wistar-Kyoto rats (WKY) were normotensive controls. Glomerular and tubulointerstitial damage, systolic blood pressure, and proteinuria were higher, and creatinine clearance was lower in SHR vs. SHR+Los and WKY. In SHR+Amlo, blood pressure was similar to WKY, kidney function was similar to SHR, and renal lesions were lower than in SHR, but higher than in SHR+Los. In kidney mitochondria from SHR and SHR+Amlo, membrane potential, nitric oxide synthase, manganese-superoxide dismutase and cytochrome oxidase activities, and uncoupling protein-2 content were lower than in SHR+Los and WKY. In SHR and SHR+Amlo, mitochondrial H2O2 production was higher than in SHR+Los and WKY. Renal glutathione content was lower in SHR+Amlo relative to SHR, SHR+Los, and WKY. In SHR and SHR+Amlo, glutathione was relatively more oxidized than in SHR+Los and WKY. Tubulointerstitial α-smooth muscle actin labeling was inversely related to manganese-superoxide dismutase activity and uncoupling protein-2 content. These findings suggest that oxidant stress is associated with renal mitochondrial dysfunction in SHR. The mitochondrial-antioxidant actions of losartan may be an additional or alternative way to explain some of the beneficial effects of AT1-receptor antagonists.

Altered gene expression of uncoupling protein-2 and -3 in stroke-prone spontaneously hypertensive rats

2000 ◽  
Vol 18 (9) ◽  
pp. 1233-1238 ◽  
Author(s):  
Yasutomo Fukunaga ◽  
Hiroshi Itoh ◽  
Kiminori Hosoda ◽  
Kentaro Doi ◽  
Junichi Matsuda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spontaneously Hypertensive Rats ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Altered Gene Expression ◽  
Altered Gene

Elevated tyrosine hydroxylase mRNA levels in medulla oblongata of spontaneously hypertensive rats

1996 ◽  
Vol 36 (1) ◽  
pp. 197-199 ◽  
Author(s):  
Toshio Kumai ◽  
Masami Tanaka ◽  
Minoru Watanabe ◽  
Hironori Nakura ◽  
Tomonori Tateishi ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Medulla Oblongata ◽  
Spontaneously Hypertensive Rats ◽  
Mrna Levels ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Propofol Protects Against Hemorrhagic Shock-Induced Organ Damage in Conscious Spontaneously Hypertensive Rats

2009 ◽  
Vol 11 (2) ◽  
pp. 152-162 ◽  
Author(s):  
Chung-Jen Lee ◽  
Ru-Ping Lee ◽  
Yi-Maun Subeq ◽  
Chia-Chi Lee ◽  
Tai-Chu Peng ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Spontaneously Hypertensive Rats ◽  
Low Dose ◽  
Organ Damage ◽  
Interleukin 10 ◽  
High Dose ◽  
Hypertensive Rats ◽  
Total Blood ◽  
Spontaneously Hypertensive ◽  
Blood Withdrawal

Patients with hypertension have higher mortality rates from hemorrhagic shock (HS) than normotensive patients. Several inflammatory mediators such as tumor necrosis factor a (TNF-a) and interleukin 10 (IL-10) can be produced by HS and lead to multiple organ dysfunction and death. We investigated the effects of high dose (10 mg/kg/hr) and low dose (1 mg/kg/hr) propofol treatment after HS in conscious spontaneously hypertensive rats (SHRs). By withdrawing 40% of total blood volume from a femoral arterial catheter (6 ml/100 g body weight [BW]) for more than 30 min, HS was induced. The mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 24 hr after the start of blood withdrawal. Levels of biochemical parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), creatine phosphokinase (CPK), and lactic dehydrogenase (LDH) were measured 30 min before and 0, 1, 3, 6, 9, 12, 18, and 24 hr after the 30-min blood withdrawal period. Cytokine levels, including TNF-a and IL-10 in the serum, were measured 1 hr after HS. The kidney, liver, and lung were removed for pathology assessment at 48 hr after HS. HS significantly increased blood GOT, GPT, BUN, LDH, CPK, TNF-a, and IL-10 levels in conscious SHRs. Posttreatment propofol decreased serum TNF-a level, increased serum IL-10 level, attenuated the severity of organ damage, and improved survival rate after HS. This treatment protected SHRs against HS-induced organ damage. Moreover, high-dose propofol had a more protective effect than low-dose propofol against HS in conscious SHRs.

scholarly journals Interleukin-1βAccelerates the Onset of Stroke in Stroke-Prone Spontaneously Hypertensive Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Tsuyoshi Chiba ◽  
Tatsuki Itoh ◽  
Masaki Tabuchi ◽  
Toru Nakazawa ◽  
Takao Satou
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Immune Cell ◽  
Stroke Onset ◽  
Blood Levels ◽  
Hypertensive Rats ◽  
Gene Expressions ◽  
Continuous Administration ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Wistar Kyoto

High blood levels of inflammatory biomarkers and immune cells in stroke lesions have been recognized as results of stroke. However, recent studies have suggested that inflammation occurs prior to stroke onset. In this study, we aimed to clarify the role of inflammation in stroke onset among stroke-prone spontaneously hypertensive rats (SHRSP). At 4 weeks of age (before stroke onset), the plasma level of IL-1βwas significantly higher in SHRSP (153.0±49.7 pg/ml) than in Wistar Kyoto rats (WKY) (7.7±3.4 pg/ml,P<0.001versus SHRSP) or spontaneously hypertensive rats (SHR) (28.0±9.1 pg/ml,P<0.001versus SHRSP) (n=6per strain). Stimulated IL-1βsignal was also observed in cerebrovascular endothelial cells of SHRSP. Gene expressions of IL-1β, IL-1 receptors, caspase-1, and downstream genes (MCP-1 and ICAM-1), which associated with immune cell recruitment, were significantly greater in SHRSP than in WKY or SHR, coincident with greater NFκB protein levels in SHRSP compared to WKY or SHR. In addition, continuous administration of IL-1β(2 μg/day) using an osmotic pump slightly increased the incidence of stroke in SHR (P=0.046) and significantly accelerated the onset of stroke in SHRSP (P=0.006) compared to each control (n=10per group). These results suggest that a stimulated IL-1βsignal might be a cause of stroke onset when concomitant with severe hypertension.

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