Angiotensin-converting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats

Kuno, Atsushi; Yamada, Tamaki; Masuda, Kazuhiko; Ogawa, Kumiko; Sogawa, Mitsue; Nakamura, Soichi; Nakazawa, Takahiro; Ohara, Hirotaka; Nomura, Tomoyuki; Joh, Takashi; Shirai, Tomoyuki; Itoh, Makoto

doi:10.1053/gast.2003.50147

Cited by 110 publications

(85 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies in obese patients suggest that weight gain itself activates the RAS (35). Pancreatic inflammation may also result in upregulation of the local RAS as demonstrated in animal models of pancreatitis (36). However, we saw no evidence of insulitis in this model.…”

Section: Discussionmentioning

confidence: 40%

“…In other tissues, blockade of the RAS seems to result in reduced fibrosis through inhibition of TGF-␤1 (20). In models of rodent pancreatitis, blockade of the RAS results in lower levels of TGF-␤ and fibrosis (36). It is conceivable that the reduction in islet fibrosis observed in this study after treatment with perindopril and irbesartan may be mediated through a similar pathway.…”

Section: Discussionmentioning

confidence: 55%

“…We report here the increased expression of TGF-␤ mRNA and protein in the islets of ZDF rats (Table 3). TGF-␤ has been previously associated with fibrosis after pancreatitis (36,46) and autoimmune diabetes (47). However, this is the first description of increased islet expression of TGF-␤ associated with a model of type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Improved Islet Morphology after Blockade of the Renin- Angiotensin System in the ZDF Rat

et al. 2004

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) has an important role in the endocrine pancreas. Although angiotensin II has significant effects on cell proliferation and apoptosis, the contribution of the RAS to changes in islet structure and function associated with type 2 diabetes is yet to be defined. This study examined the specific effects of RAS blockade on islet structure and function in diabetes. Thirty-six male Zucker diabetic fatty (ZDF) rats, 10 weeks of age, were randomized to receive the angiotensin-converting enzyme inhibitor perindopril (8 mg/l in drinking water; n ‫؍‬ 12), irbesartan (15 mg/kg via gavage; n ‫؍‬ 12), or no treatment (n ‫؍‬ 12) for 10 weeks. Results were compared with lean littermates (ZL) (n ‫؍‬ 12) studied concurrently. ZDF rats had increased intraislet expression of components of the RAS correlating with increased intraislet fibrosis, apoptosis, and oxidative stress. Disordered islet architecture, seen in ZDF rats, was attenuated after treatment with perindopril or irbesartan. Islet fibrogenesis was also diminished, as measured by picrosirius staining and expression of collagens I and IV. Gene expression of transforming growth factor-␤1 was increased in the ZDF pancreas (ZL, 1.0 ؎ 0.1; ZDF, 2.0 ؎ 0.3; P < 0.05) and reduced after blockade of the RAS (ZDF ؉ P, 1.3 ؎ 0.2; ZDF ؉ I, 1.5 ؎ 0.1; vs. ZDF, both P < 0.05). Improvements in structural parameters were also associated with functional improvements in first-phase insulin secretion. These findings provide a possible mechanism for the reduced incidence of new-onset diabetes that has been observed in clinical trials of RAS blockade. Diabetes 53: 989 -997, 2004

show abstract

Section: Discussionmentioning

confidence: 40%

Section: Discussionmentioning

confidence: 55%

See 1 more Smart Citation

Improved Islet Morphology after Blockade of the Renin- Angiotensin System in the ZDF Rat

et al. 2004

View full text Add to dashboard Cite

show abstract

“…[13][14][15] The renin-angiotensin system plays an important role in causing SMC fibrosis, and angiotensin II type I receptor blockers and angiotensin-sconverting enzyme inhibitors can ameliorate SMC fibrosis and extend the life span of SMCs in animal models. [16][17][18][19] Tankyrase 1 also has a similar effect. 14,15 This study determined that a decrease in erectile function coincided with the downregulation of SMC proliferation and SMC/CF proportions in diabetic ED rats and that icarisid II could ameliorate these effects.…”

Section: Discussionmentioning

confidence: 82%

Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, mTOR and the NO–cGMP pathway

Zhang¹,

Li²,

Liu³

et al. 2012

Asian J Androl

View full text Add to dashboard Cite

Erectile dysfunction (ED) is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid II. This study investigates the effects of icarisid II on diabetic rats with ED and its potential mechanism via the assessment of advanced glycosylation end products (AGEs), autophagy, mTOR and the NO-cGMP pathway. Icarisid II was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid II group, rats were administered icarisid II intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure (ICP/MAP). AGE concentrations, nitric oxide synthase (NOS) activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 localisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid II increased ICP/MAP values, the smooth muscle cell (SMC) growth curve, S phase and SMC/collagen fibril (SMC/CF) proportions and decreased Beclin 1 (P,0.05). Icarisid II significantly increased the proliferative index and p-p70S6K(Thr389) levels and decreased the numbers of autophagosomes and the levels of LC3-II (P,0.01). Icarisid II decreased AGE concentrations and increased cGMP concentration, NOS activity (P,0.05) and cNOS levels (P,0.01) in the diabetic ED group. Therefore, Icarisid II constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.

show abstract

“…Recent studies have shown that the reninangiotensin system (RAS) components were upregulated in acute pancreatitis which may induce oxidative stress and pancreatic, exocrine secretion (Tsang et al 2004). Inhibition of RAS by ACE blocker could attenuate pancreatic inflammation (Kuno et al 2003). On the other hand, captopril could cause acute pancreatitis (Iliopoulou et al 2001).…”

mentioning

confidence: 99%

Captopril, an Angiotensin-Converting Enzyme Inhibitor, Attenuates the Severity of Acute Pancreatitis in Rats by Reducing Expression of Matrix Metalloproteinase 9

Chen

Yuan

Wang

et al. 2006

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

It has been reported that matrix metalloproteinase 9 (MMP-9) disrupts basement membrane and increases vascular permeability. MMP-9 therefore might participate in the pathogenesis of severe acute pancreatitis (SAP). Captopril, an angiotensin-converting enzyme inhibitor, could reduce MMP-9 expression. However, the effect of captopril on the outcome of SAP is not ascertained. The aim of this study was to determine whether captopril attenuates the severity of SAP by reducing MMP-9 expression. Thirty SpragueDawley rats were randomly divided into 3 groups (n = 10 for each). Rats were given intraperitoneal injection of saline (SAP group) or captopril (4 mg/kg) (treated group), and then given retrograde infusion of 5% sodium taurocholate (1.5 ml/kg) into the pancreatic duct under laparotomy to induce SAP. One group of rats, injected with saline, underwent only sham operation (Control). Experimental samples were collected at 24 hrs after the induction of SAP or sham operation. Various markers of severity of SAP, such as serum levels of amylase and trypsinogen activation peptide and the vascular permeability, were increased in rats with SAP, but were significantly decreased in captopril-treated rats ( p < 0.01). Likewise, the serum MMP-9 levels and expression levels of pancreatic tissue MMP-9 were significantly higher in rats with SAP than those in captopril-treated rats and control rats ( p < 0.01 for both parameters), but showed no difference between captopriltreated and control rats. These results suggest that captopril may attenuate vascular permeability by reducing MMP-9 expression in SAP, thereby ameliorating severity of the disease. The use of captopril might become a new therapeutic agent for SAP. matrix metalloproteinase-9; captopril; severe acute pancreatitis

show abstract

Angiotensin-converting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats

Cited by 110 publications

References 43 publications

Improved Islet Morphology after Blockade of the Renin- Angiotensin System in the ZDF Rat

Improved Islet Morphology after Blockade of the Renin- Angiotensin System in the ZDF Rat

Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, mTOR and the NO–cGMP pathway

Captopril, an Angiotensin-Converting Enzyme Inhibitor, Attenuates the Severity of Acute Pancreatitis in Rats by Reducing Expression of Matrix Metalloproteinase 9

Contact Info

Product

Resources

About