Sulfur-Containing Angiotensin-Converting Enzyme Inhibitor 3-Thienylalanine-Ornithyl-Proline Activates Endothelial Function and Expression of Genes Involved in Renin–Angiotensin System

In Japan, only about 3% of all patients with end-stage renal disease are maintained by continuous ambulatory peritoneal dialysis (CAPD). Although the reasons for the low proportion of patients receiving CAPD are multifactorial, encapsulating peritoneal sclerosis (EPS), a fatal complication of CAPD, is a major factor. In 1995 we developed a rat model of EPS, and in 2001 also developed an EPS model in mice. These rodent EPS models are reliable, reproducible, and inexpensive and have been used by other investigators. The renin–angiotensin system negatively regulates the transforming growth factor-beta signaling pathway, which plays a major role in tissue fibrosis. To investigate the anti-EPS effect of renin–angiotensin system inhibition, an angiotensin-converting enzyme inhibitor, quinapril, was administered to an EPS model in mice. Quinapril was found to inhibit EPS, both macro- and microscopically, in a dose-dependent manner. We report our experience of developing the experimental in vivo EPS model, and the inhibitory effect of this angiotensin-converting enzyme inhibitor on EPS.

Download Full-text

Effects of chronic administration of spirapril, a new angiotensin converting enzyme inhibitor, on blood pressure and renin-angiotensin system in normotensive rats

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)55758-4 ◽

1990 ◽

Vol 52 ◽

pp. 312

Author(s):

Hamao Toda ◽

Hisayo Oohata ◽

Takeshi Suzuki ◽

Kazuko Fujimoto ◽

Koichiro Kawashima

Keyword(s):

Blood Pressure ◽

Angiotensin Converting Enzyme ◽

Angiotensin Converting Enzyme Inhibitor ◽

Enzyme Inhibitor ◽

Renin Angiotensin System ◽

Chronic Administration ◽

Converting Enzyme ◽

Angiotensin System ◽

Renin Angiotensin ◽

Converting Enzyme Inhibitor

Download Full-text

The angiotensin-converting enzyme inhibitor captopril rescues mice from endotoxin-induced lethal hepatitis

Innate Immunity ◽

10.1177/1753425916680037 ◽

2016 ◽

Vol 23 (2) ◽

pp. 128-135 ◽

Cited By ~ 2

Author(s):

Pu Ge ◽

Rong Jiang ◽

Xin Yao ◽

Jing Li ◽

Jie Dai ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Angiotensin Converting Enzyme Inhibitor ◽

Fulminant Hepatitis ◽

Enzyme Inhibitor ◽

Renin Angiotensin System ◽

Converting Enzyme ◽

Angiotensin System ◽

Renin Angiotensin ◽

Converting Enzyme Inhibitor ◽

Tnf Α

The renin–angiotensin system is classically regarded as a crucial regulator of circulatory homeostasis, but recent studies also revealed its pro-inflammatory roles. The beneficial effects of the angiotensin-converting enzyme inhibitor (ACEI) in severe inflammatory injury in the lung and heart have been previously reported, but its potential effects on lethal hepatitis were unknown. In this study, a mouse model with LPS/d-galactosamine (GalN)-induced fulminant hepatitis were used to test the protective potential of captopril, a representative ACEI. The results indicated that treatment with captopril significantly decreased the plasma level of alanine aminotransferase and aspartate aminotransferase, alleviated the histopathological damage of the liver tissue and improve the survival rate of LPS/GalN-challenged mice. These effects were accompanied by reduced mRNA levels of TNF-α and IL-6 in the liver, and decreased protein level of TNF-α and IL-6 in the plasma. In addition, the activation of caspases 3, 8 and 9, and the presence of TUNEL-positive apoptotic cells, were also suppressed by captopril treatment. The above evidence suggested that the renin–angiotensin system might be involved in the development of LPS/GalN-induced fulminant hepatitis and ACEI might have potential value in lethal hepatitis.

Download Full-text