Angiotensin II Type 1 Receptor Blocker Reduces Monocyte Adhesion to Endothelial Cells in Spontaneously Hypertensive Rats

Ikeda, Fuki; Azuma, Kosuke; Ogihara, Takeshi; Toyofuku, Yukiko; Otsuka, Aiko; Mita, Tomoya; Hirose, Takahisa; Tanaka, Yasushi; Kawamori, Ryuzo; Watada, Hirotaka

doi:10.1507/endocrj.k07-004

Cited by 7 publications

(3 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, valsartan significantly inhibited adipose tissue macrophage infiltration and inflammation in rats treated by long-term high-fat diet [31]. In addition, valsartan has been shown to reduce CD68-stained cell adhesion to endothelial cell in spontaneously hypertensive rats [32]. Therefore, the antiinflammatory effect of ARNI and ARB might be contributed mainly by the blockade of angiotensin.…”

Section: Discussionmentioning

confidence: 94%

Dual Angiotensin Receptor and Neprilysin Inhibitor Ameliorates Portal Hypertension in Portal Hypertensive Rats

et al. 2020

View full text Add to dashboard Cite

Background: Portal hypertension is characterized by exaggerated activation of the renin-angiotensin-aldosterone axis. Natriuretic peptide system plays a counter-regulatory role, which is modulated by neprilysin. LCZ696 (sacubitril/valsartan) is a dual angiotensin receptor and neprilysin inhibitor. This study evaluated the effect of LCZ696 on portal hypertensive rats. Methods: Portal hypertension was induced by partial portal vein ligation (PVL) in rats. LCZ696, valsartan (angiotensin receptor blocker), or normal saline (control) was administered in PVL rats for 10 days. Then, hemodynamic and biochemistry data were obtained. The hepatic histology and protein expressions were surveyed. On the parallel groups, the portal-systemic shunting degrees were determined. Results: LCZ696 and valsartan reduced mean arterial pressure and systemic vascular resistance. LCZ696, but not valsartan, reduced portal pressure in portal hypertensive rats (control vs. valsartan vs. LCZ696: 15.4 ± 1.6 vs. 14.0 ± 2.3 vs. 12.0 ± 2.0 mmHg, control vs. LCZ696: P < 0.05). LCZ696 and valsartan improved liver biochemistry data and reduced intrahepatic Cluster of Differentiation 68 (CD68)-stained macrophages infiltration. Hepatic endothelin-1 (ET-1) protein expression was downregulated by LCZ696. The portal-systemic shunting was not affected by LCZ696 and valsartan. Conclusion: LCZ696 and valsartan reduced mean arterial pressure through peripheral vasodilation. Furthermore, LCZ696 significantly reduced portal pressure in PVL rats via hepatic ET-1 downregulation.

show abstract

Section: Discussionmentioning

confidence: 94%

Dual Angiotensin Receptor and Neprilysin Inhibitor Ameliorates Portal Hypertension in Portal Hypertensive Rats

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Aortic inflammation and loss of vascular smooth muscle cells (VSMCs) are two hallmark features of AAA pathology [2]. Hydralazine, an antihypertensive medication, has been shown to inhibit inflammation [8,9] in various disease models (spinal cord injury [10], kidney injury [11], and sepsis [12]), and also limit apoptosis of cardiomyocytes [13]. Whether hydralazine inhibits the apoptosis of VSMCs is unknown.…”

Section: Introductionmentioning

confidence: 99%

Effect of Hydralazine on Angiotensin II-Induced Abdominal Aortic Aneurysm in Apolipoprotein E-Deficient Mice

Wang,

Sargisson,

Nguyen

et al. 2023

IJMS

View full text Add to dashboard Cite

The rupture of an abdominal aortic aneurysm (AAA) causes about 200,000 deaths worldwide each year. However, there are currently no effective drug therapies to prevent AAA formation or, when present, to decrease progression and rupture, highlighting an urgent need for more research in this field. Increased vascular inflammation and enhanced apoptosis of vascular smooth muscle cells (VSMCs) are implicated in AAA formation. Here, we investigated whether hydralazine, which has anti-inflammatory and anti-apoptotic properties, inhibited AAA formation and pathological hallmarks. In cultured VSMCs, hydralazine (100 μM) inhibited the increase in inflammatory gene expression and apoptosis induced by acrolein and hydrogen peroxide, two oxidants that may play a role in AAA pathogenesis. The anti-apoptotic effect of hydralazine was associated with a decrease in caspase 8 gene expression. In a mouse model of AAA induced by subcutaneous angiotensin II infusion (1 µg/kg body weight/min) for 28 days in apolipoprotein E-deficient mice, hydralazine treatment (24 mg/kg/day) significantly decreased AAA incidence from 80% to 20% and suprarenal aortic diameter by 32% from 2.26 mm to 1.53 mm. Hydralazine treatment also significantly increased the survival rate from 60% to 100%. In conclusion, hydralazine inhibited AAA formation and rupture in a mouse model, which was associated with its anti-inflammatory and anti-apoptotic properties.

show abstract

“…Recently, we established a new en face method for optimal observation of endothelial surface (NEMOes), which is suitable for quantification of the number of monocytes that adhere to rat thoracic aorta after immunostaining for the monocyte/ macrophage-specific protein, CD68 [13][14][15][16]. In a series of studies, we used NEMOes to investigate endothelial function in the Goto-Kakizaki (GK) rat, a genetic non-obese type 2 diabetes rat fed twice daily as a model of repetitive postprandial hyperglycemia [17].…”

mentioning

confidence: 99%

Repetitive Postprandial Hypertriglyceridemia Induces Monocyte Adhesion to Aortic Endothelial Cells in Goto-Kakizaki Rats

et al. 2008

Self Cite

View full text Add to dashboard Cite

Abstract. To compare the effects of postprandial hypertriglyceridemia and postprandial hyperglycemia on monocyte adhesion to endothelial cells, we investigated the effects of twice-daily standard diet (5% fat) and high-fat diet (30% fat) for 3 weeks on monocyte adhesion to endothelial cells and the expression of adhesion molecules in the aortic artery in nonobese type 2 diabetic Goto-Kakizaki rats. Fasting glucose, insulin, non-esterified fatty acid (NEFA), HbA1c, and body weight were comparable between the two diet groups. Postprandial glucose and insulin were higher in the standard diet group, while postprandial NEFA and triglyceride were higher in the high fat diet group, compared with the other group. The number of monocyte adherent to endothelial cells was higher in the high-fat diet group than the standard diet group. Consumption of high-fat diet resulted in overexpression of heme oxygenase-1, intercellular adhesion molecule-1 (ICAM-1), and connecting segment-1 fibronectin on the arterial wall, compared with standard diet. Thus, our data demonstrated that short-term intermittent high-fat diet prevented postprandial hyperglycemia in a model of type 2 diabetes without a significant increase in body weight. However, the resulting postprandial hypertriglyceridemia induces more monocyte adhesion to endothelial cells than postprandial hyperglycemia. This increased monocyte adhesion is associated with the increased aortic expression of adhesion molecules such as ICAM-1, and connecting segment-1 fibronectin.

show abstract

Angiotensin II Type 1 Receptor Blocker Reduces Monocyte Adhesion to Endothelial Cells in Spontaneously Hypertensive Rats

Cited by 7 publications

References 26 publications

Dual Angiotensin Receptor and Neprilysin Inhibitor Ameliorates Portal Hypertension in Portal Hypertensive Rats

Dual Angiotensin Receptor and Neprilysin Inhibitor Ameliorates Portal Hypertension in Portal Hypertensive Rats

Effect of Hydralazine on Angiotensin II-Induced Abdominal Aortic Aneurysm in Apolipoprotein E-Deficient Mice

Repetitive Postprandial Hypertriglyceridemia Induces Monocyte Adhesion to Aortic Endothelial Cells in Goto-Kakizaki Rats

Contact Info

Product

Resources

About