Inhibition of renin-angiotensin system in experimental acute pancreatitis in rats: A new therapeutic target?

Oruç, Nevin; Özütemiz, Ömer; Nart, Denız; Yüce, Gül; Celik, Handan; İlter, Tankut

doi:10.1016/j.etp.2009.05.001

Cited by 19 publications

(17 citation statements)

References 32 publications

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“…[26][27][28][29] The studies have shown the critical role of the renin-angiotensin system in the development of pancreatic neuropathy in experimental acute/chronic pancreatitis models as well in clinical pancreatitis. 8,30,31 In our previous study, telmisartan was reported to attenuate neuropathic pain behavior in the CCI model. 15 This is the first experimental study reporting the potential of aliskiren, a direct renin inhibitor, in attenuating neuropathic pain manifestations in the CCI model.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6] The blocking of the renin-angiotensin-aldosterone pathway is an important approach in various neurodegenerative diseases and conditions such as migraine pain, nociceptive pain and pancreatic pain. [7][8][9] Aliskiren blocks the reninangiotensin-aldosterone system by directly inhibiting renin and, subsequently, decreases the production of biologically active angiotensin neuropeptides, including angiotensin II. Studies have shown the usefulness of renin inhibitors in hypertension, atherosclerosis, chronic kidney disease, cardiac hypertrophy and vascular inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Neuropathic pain-attenuating potential of aliskiren in chronic constriction injury model in rats

Kukkar

Singh

Jaggi

2012

J Renin Angiotensin Aldosterone Syst

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The present study was designed to investigate the potential of aliskiren, a direct renin inhibitor, in chronic constriction injury (CCI)-induced neuropathic pain in rats. Neuropathic pain was induced by placing four loose ligatures around the sciatic nerve. Acetone drop, von Frey hair, pin-prick and hot plate tests were performed to assess cold allodynia, mechanical allodynia, mechanical and heat hyperalgesia, respectively. The levels of Tumor necrosis factor-alpha (TNFa) were measured in the sciatic nerve as an inflammatory marker. CCI was associated with the development of cold allodynia, mechanical allodynia, mechanical and heat hyperalgesia along with a rise in the levels of Tumor necrosis factoralpha (TNF-a). Administration of aliskiren (25 or 50 mg/kg intraperitoneal (i.p.)) for 14 days in CCI-subjected rats significantly attenuated CCI-induced pain-related behavior and rise in TNF-a level. It may be concluded that aliskiren-mediated anti-inflammatory actions may be responsible for its beneficial effects in neuropathic pain in rats.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuropathic pain-attenuating potential of aliskiren in chronic constriction injury model in rats

Kukkar

Singh

Jaggi

2012

J Renin Angiotensin Aldosterone Syst

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“…First, the local renin-angiotensin system in the pancreas plays an important role in regulation of pancreatic acinar cell digestive enzyme secretion and pancreatic ducts 38–40. In animal models, losartan may decrease pancreatic parenchymal necrosis and neutrophil infiltration, inhibit acinar digestive enzyme secretion and further ameliorate the pancreatic injury in experimental acute pancreatitis 38 41 42. These data suggest that losartan may protect against acute pancreatitis, which can partially explain why previous epidemiological studies have shown that losartan use is associated with a non-significantly reduced risk of acute pancreatitis 36 37.…”

Section: Discussionmentioning

confidence: 71%

No association between losartan use and acute pancreatitis in hypertensive patients

Lai

Lin

et al. 2016

Eur J Hosp Pharm

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Background and objectiveClinical evidence is scarce about the relationship between losartan use and acute pancreatitis. We therefore conducted a population-based case–control study using the database from the Taiwan National Health Insurance Program to investigate this question.MethodsThe study consisted of 1449 hypertensive subjects aged 20–84 years with a first episode of acute pancreatitis during the period 2000–2011 as the case group and 2479 hypertensive subjects without acute pancreatitis as the control group. Both the case and control groups were matched for sex, age, comorbidities and index year of acute pancreatitis diagnosis. According to the history of losartan prescription before the date of diagnosis of acute pancreatitis, subjects who had never received a prescription for losartan were defined as ‘never use of losartan’, those whose last remaining losartan tablet was detected within 7 days before the date of diagnosis of acute pancreatitis were defined as ‘current use of losartan’ and those whose last remaining tablet of losartan was detected ≥8 days before the date of diagnosis of acute pancreatitis were defined as ‘late use of losartan’. ORs and 95% CIs were measured to investigate the risk of acute pancreatitis associated with losartan use by the multivariable unconditional logistic regression model.ResultsAfter adjustment for potentially confounding factors, the adjusted OR of acute pancreatitis was 0.96 (95% CI 0.68 to 1.37) for subjects with current use of losartan compared with those with never use of losartan, but the difference was not statistically significant. For subjects with late use of losartan the adjusted OR of acute pancreatitis was 1.05 (95% CI 0.80 to 1.37), which also was not statistically significant.ConclusionsNo significant association can be detected between losartan use and acute pancreatitis in hypertensive patients. More research is required to determine the potential role of losartan in the risk of acute pancreatitis.

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“…Leung et al (10) revealed that experimental pancreatitis induced upregulation of several key RAS components in the pancreas. Several other studies have reported that RAS blockers are effective in the treatment of experimental pancreatitis (21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Concentration of tissue angiotensin II increases with severity of experimental pancreatitis

Furukawa

Shinmura

Tajima

et al. 2013

Molecular Medicine Reports

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Abstract. Necrotizing pancreatitis is a serious condition that is associated with high morbidity and mortality. Although vasospasm is reportedly involved in necrotizing pancreatitis, the underlying mechanism is not completely clear. In addition, the local renin-angiotensin system has been hypothesized to be involved in the progression of pancreatitis and trypsin has been shown to generate angiotensin II under weakly acidic conditions. However, to the best of our knowledge, no studies have reported elevated angiotensin II levels in tissue with pancreatitis. In the present study, the concentration of pancreatic angiotensin II in rats with experimentally induced acute pancreatitis was measured. Acute pancreatitis was induced by retrograde injection of 6% sodium taurocholate into the biliopancreatic duct. Control rats were sacrificed without injection into the biliopancreatic duct. The concentration of tissue angiotensin II was measured using the florisil method. Angiotensin II concentration in tissues with acute pancreatitis measured at 3, 6, 12 and 24 h following taurocholate injection were significantly higher than that of normal pancreatic tissue. In addition, the concentration of angiotensin II increased in a time-dependent manner. The results demonstrated that the angiotensin II generating system is involved in the transition from edematous to necrotizing pancreatitis in experimental animals. We hypothesize that locally formed angiotensin II affects the microenvironment in pancreatitis.

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Inhibition of renin-angiotensin system in experimental acute pancreatitis in rats: A new therapeutic target?

Cited by 19 publications

References 32 publications

Neuropathic pain-attenuating potential of aliskiren in chronic constriction injury model in rats

Neuropathic pain-attenuating potential of aliskiren in chronic constriction injury model in rats

No association between losartan use and acute pancreatitis in hypertensive patients

Concentration of tissue angiotensin II increases with severity of experimental pancreatitis

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