Vasopeptidase Inhibition Prevents Target Organ Damage and Improves Survival in Spontaneously Hypertensive Rats

Blood pressure variability (BPV) is associated with the development and progression of severe target organ damage (TOD). This study aims to evaluate the protective effect of paeoniflorin enriched extract from Radix Paeoniae Alba (PG) on BPV and TOD in spontaneously hypertensive rats (SHR). All SHR were orally treated with distilled water, metoprolol (MP, 20 mg/kg), and PG (PG-H, 90 mg/kg or PG-L, 30 mg/kg) for a single time or daily for 7 weeks. The 24-hour dynamic blood pressure was monitored and then calculated BPV including long- and short-term systolic blood pressure variability (SBPV), diastolic blood pressure variability (DBPV), mean blood pressure variability (MBPV), and heart rate variability (HRV) as well as the 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP. The protective effects of PG on TOD were observed by histopathologic and biochemical detection. The results indicated that long- and short-term SBPV, DBPV, MBPV, and HRV as well as 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP showed no significant changes after single-dose administration of PG and significantly decreased after administration with PG for 7 weeks. PG could also markedly improve the damage of aorta, heart, kidney, and brain. This study suggested that PG could notably reduce BPV, stabilize blood pressure, and mitigate TOD in SHR.

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Continuous inhibition of the renin–angiotensin system and protection from hypertensive end-organ damage by brief treatment with angiotensin II type 1 receptor blocker in stroke-prone spontaneously hypertensive rats

Life Sciences ◽

10.1016/j.lfs.2004.12.048 ◽

2005 ◽

Vol 77 (18) ◽

pp. 2233-2245 ◽

Cited By ~ 14

Author(s):

Kumiko Takemori ◽

Hiroyuki Ishida ◽

Hiroyuki Ito

Keyword(s):

Angiotensin Ii ◽

Spontaneously Hypertensive Rats ◽

Renin Angiotensin System ◽

Organ Damage ◽

Receptor Blocker ◽

Brief Treatment ◽

Hypertensive Rats ◽

Angiotensin System ◽

Spontaneously Hypertensive

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

International Journal of Molecular Sciences ◽

10.3390/ijms21124289 ◽

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.

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

Biological Research For Nursing ◽

10.1177/1099800409334750 ◽

2009 ◽

Vol 11 (2) ◽

pp. 152-162 ◽

Cited By ~ 7

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.

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