The inhibitory effects of captopril on the growth of various cultured cells

Nagai, Makoto; Arino, Tohru; Tsuchiya, Masahito; Takeda, Nobuakira; Nagano, Makoto

doi:10.1016/0022-2828(92)90756-p

Cited by 2 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that another ACE-I, captopril, inhibited the growth of fibroblasts in vitro. 29 It also reduced collagen accumulation in the pig serum-induced liver fibrosis model. 30 However, the degree of inhibitory effect of captopril on hepatic hydroxyproline accumulation was almost half of that of PE and CA in the present study.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats

2001

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) is frequently activated in patients with chronic liver diseases. Angiotensin-II (AT-II) has been suggested to play an important role in liver fibrogenesis. It induces hepatic stellate cell (HSC) proliferation and up-regulates the transforming growth factor 1 (TGF-1) expression via AT-II type 1 receptor (AT 1-R) in vitro. The aim of the present study was to examine the in vivo effect of candesartan (CA), a clinically used AT 1-R blocker (ARB), and perindopril (PE), an angiotensin-converting enzyme (ACE) inhibitor (ACE-I), on pig serum-induced liver fibrosis development in rats. The clinically available comparable doses of CA and PE significantly attenuated the fibro-sis development. These inhibitory effects of PE and CA were also found in the ongoing liver fibrosis model. The hepatic hydroxyproline and serum fibrosis markers were significantly suppressed by CA and PE treatment. Furthermore, the smooth muscle actin (-SMA) positive cells in number were markedly suppressed by CA and PE treatment. Similarly , the hepatic TGF-1 protein and messenger RNA (mRNA) levels were significantly suppressed. Our in vitro study showed that AT-II increased the TGF-1 mRNA expression in the activated HSCs, and this effect was totally blocked by CA. These results suggested that the RAS, especially AT-II and AT 1-R interaction plays a pivotal role in liver fibrosis development through HSC activation. Because both CA and PE are widely used in clinical practice without serious side effects, these drugs may provide an effective new strategy for anti-liver fibrosis therapy. (HEPATOLOGY 2001; 34:745-750.) The renin-angiotensin system (RAS) is reportedly activated in patients with chronic liver diseases, such as cirrhosis. 1-3 Angiotensin-II (AT-II), which is an octapeptide produced mainly by proteolytic cleavage of its precursor AT-I by angio-tensin-converting enzyme (ACE), has many physiologic effects , including vascular hormonal secretion, tissue growth, and neuronal activities. 4,5 AT-II is also considered a potential mediator of intrahepatic portal hypertension, because its plasma level was increased in patients with cirrhosis, and its administration induced elevation of the portal pressure. 6,7 To date, several types of AT-II receptors have been identified. 5 The AT-II type 1 receptor (AT 1-R) mediates most of the biological effects of AT-II, including increase in the intracellular Ca 2 concentration, cell contraction, and proliferation. 5 Recently , losartan, which is used clinically as an AT 1-R antagonist , has been shown to reduce the portal pressure in hepatic cirrhosis. 8 It has been revealed that AT-II induced contraction and proliferation of hepatic stellate cells (HSCs). 9 AT-II also increased the transforming growth factor 1 (TGF-1) and collagen-I gene expression in the fibroblasts in vitro. 10-12 These biological actions were mediated predominantly through AT 1-R. Accordingly, AT-II and AT 1-R interaction seems to have a pivotal role in liver fibrosis development. Evidence that these mole...

show abstract

Section: Discussionmentioning

confidence: 99%

Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats

2001

View full text Add to dashboard Cite

show abstract

Captopril reduces collagen and mast cell and eosinophil accumulation in pig serum‐induced rat liver fibrosis

Ramos

Montenegro

Góissis

et al. 1994

Pathology International

View full text Add to dashboard Cite

The effect of captopril on the development of hepatic septal fibrosis in a specific experimental model produced by repeated injections of whole pig serum into the peritoneal cavity of rats was studied. The results afforded four basic conclusions. First, the experimental model used seems to be a pure form of septal fibrosis, which depends on active tissue fibroplasia, without hepatocyte necrosis. The fibrotic septa, located between limiting plates of adjacent classic hepatic lobules, and delimiting the classic liver lobule, consisted of collagen fibers infiltrated by eosinophils, mast cells, fat‐storing cells (Ito cells), transitional cells and interstitial fibro‐blasts. Second, the angiotensin‐converting enzyme inhibitor captopril attenuated the hepatic fibrosis induced by pig serum administration, as proven by a decrease In hepatic hydroxyproline concentration and histological examination of the liver. Third, this attenuation of hepatic fibrosis might be related, at least in part, to diminished mast cell and eosinophil accumulation in the hepatic tissue. Finally, these data may indicate a novel action of angiotensin‐converting enzyme inhibitor in general, and for captopril in particular, as drugs potentially capable of reducing eosinophils in fibrotic processes.

show abstract

The inhibitory effects of captopril on the growth of various cultured cells

Cited by 2 publications

References 0 publications

Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats

Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats

Captopril reduces collagen and mast cell and eosinophil accumulation in pig serum‐induced rat liver fibrosis

Contact Info

Product

Resources

About