Contribution of Chymase-Dependent Angiotensin II Formation to the Progression of Tubulointerstitial Fibrosis in Obstructed Kidneys in Hamsters
Recent studies indicate a role of chymase in the regulation of angiotensin II (AngII) formation in cardiovascular and renal tissues. We investigated a possible contribution of chymase to AngII formation and to renal fibrosis in unilateral ureteral obstruction (UUO). Eight-week-old Syrian hamsters we...
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| Format: | Article |
| Language: | English |
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Elsevier
2009-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319311363 |
| _version_ | 1818419543397105664 |
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| author | Yu-Yan Fan Akira Nishiyama Yoshihide Fujisawa Hiroyuki Kobori Daisuke Nakano Junji Matsuura Naoki Hase Hirofumi Hitomi Hideyasu Kiyomoto Hidenori Urata Masakazu Kohno |
| author_facet | Yu-Yan Fan Akira Nishiyama Yoshihide Fujisawa Hiroyuki Kobori Daisuke Nakano Junji Matsuura Naoki Hase Hirofumi Hitomi Hideyasu Kiyomoto Hidenori Urata Masakazu Kohno |
| author_sort | Yu-Yan Fan |
| collection | DOAJ |
| description | Recent studies indicate a role of chymase in the regulation of angiotensin II (AngII) formation in cardiovascular and renal tissues. We investigated a possible contribution of chymase to AngII formation and to renal fibrosis in unilateral ureteral obstruction (UUO). Eight-week-old Syrian hamsters were subjected to UUO and treated with vehicle, the specific chymase inhibitor (CI) 4-[1-(4-methyl-benzo[b]thiophen-3-ylmethyl)-1H-benzimidazol-2-ylsulfanyl]-butyric acid (50 mg/kg, twice a day, p.o.), or the selective AT1-receptor blocker olmesartan (10 mg/kg per day, p.o.) for 14 days. UUO-induced renal interstitial fibrosis was associated with increases in renal mRNA levels of α-smooth muscle actin (SMA), type I collagen, and transforming growth factor (TGF)-β. The UUO hamsters showed markedly higher AngII contents and increased AT1-receptor mRNA level in the obstructed kidney than sham-operated ones. In contrast, angiotensin-converting enzyme (ACE) protein expression was significantly lower in UUO hamsters. In UUO hamsters, treatment with CI or olmesartan significantly decreased AngII levels in renal tissue and mRNA levels of α-SMA, type I collagen, and TGF-β and ameliorated tubulointerstitial injury. On the other hand, neither CI nor olmesartan changed systolic blood pressure, renal ACE, and AT1-receptor protein levels. These data suggest that chymase-dependent intrarenal AngII formation contributes to the pathogenesis of interstitial fibrosis in obstructed kidneys of hamsters. Keywords:: chymase, angiotensin II, angiotensin-converting enzyme, unilateral ureteral obstruction |
| first_indexed | 2024-12-14T12:40:14Z |
| format | Article |
| id | doaj.art-c5f75a5078a34115bc210c8c53aa198c |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-14T12:40:14Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-c5f75a5078a34115bc210c8c53aa198c2022-12-21T23:00:56ZengElsevierJournal of Pharmacological Sciences1347-86132009-01-0111118290Contribution of Chymase-Dependent Angiotensin II Formation to the Progression of Tubulointerstitial Fibrosis in Obstructed Kidneys in HamstersYu-Yan Fan0Akira Nishiyama1Yoshihide Fujisawa2Hiroyuki Kobori3Daisuke Nakano4Junji Matsuura5Naoki Hase6Hirofumi Hitomi7Hideyasu Kiyomoto8Hidenori Urata9Masakazu Kohno10Department of Cardiorenal and Cerebrovascular Medicine, Kagawa 761-0701, Japan; Department of Pharmacology, Kagawa 761-0701, JapanDepartment of Pharmacology, Kagawa 761-0701, JapanLife Sciences Research Center, Kagawa University Medical School, Kagawa 761-0701, JapanDepartment of Physiology, Tulane University Health Sciences Center, New Orleans, LA 70112, USADepartment of Pharmacology, Kagawa 761-0701, Japan; Corresponding author. dnakano@med.kagawa-u.ac.jpPharmacology and Safety Research Department, Teijin Institute for Biomedical Research, Teijin Pharma Ltd., Tokyo 191-8512, JapanPharmacology and Safety Research Department, Teijin Institute for Biomedical Research, Teijin Pharma Ltd., Tokyo 191-8512, JapanDepartment of Pharmacology, Kagawa 761-0701, JapanDepartment of Cardiorenal and Cerebrovascular Medicine, Kagawa 761-0701, JapanDepartment of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Fukuoka 818-8502, JapanDepartment of Cardiorenal and Cerebrovascular Medicine, Kagawa 761-0701, JapanRecent studies indicate a role of chymase in the regulation of angiotensin II (AngII) formation in cardiovascular and renal tissues. We investigated a possible contribution of chymase to AngII formation and to renal fibrosis in unilateral ureteral obstruction (UUO). Eight-week-old Syrian hamsters were subjected to UUO and treated with vehicle, the specific chymase inhibitor (CI) 4-[1-(4-methyl-benzo[b]thiophen-3-ylmethyl)-1H-benzimidazol-2-ylsulfanyl]-butyric acid (50 mg/kg, twice a day, p.o.), or the selective AT1-receptor blocker olmesartan (10 mg/kg per day, p.o.) for 14 days. UUO-induced renal interstitial fibrosis was associated with increases in renal mRNA levels of α-smooth muscle actin (SMA), type I collagen, and transforming growth factor (TGF)-β. The UUO hamsters showed markedly higher AngII contents and increased AT1-receptor mRNA level in the obstructed kidney than sham-operated ones. In contrast, angiotensin-converting enzyme (ACE) protein expression was significantly lower in UUO hamsters. In UUO hamsters, treatment with CI or olmesartan significantly decreased AngII levels in renal tissue and mRNA levels of α-SMA, type I collagen, and TGF-β and ameliorated tubulointerstitial injury. On the other hand, neither CI nor olmesartan changed systolic blood pressure, renal ACE, and AT1-receptor protein levels. These data suggest that chymase-dependent intrarenal AngII formation contributes to the pathogenesis of interstitial fibrosis in obstructed kidneys of hamsters. Keywords:: chymase, angiotensin II, angiotensin-converting enzyme, unilateral ureteral obstructionhttp://www.sciencedirect.com/science/article/pii/S1347861319311363 |
| spellingShingle | Yu-Yan Fan Akira Nishiyama Yoshihide Fujisawa Hiroyuki Kobori Daisuke Nakano Junji Matsuura Naoki Hase Hirofumi Hitomi Hideyasu Kiyomoto Hidenori Urata Masakazu Kohno Contribution of Chymase-Dependent Angiotensin II Formation to the Progression of Tubulointerstitial Fibrosis in Obstructed Kidneys in Hamsters Journal of Pharmacological Sciences |
| title | Contribution of Chymase-Dependent Angiotensin II Formation to the Progression of Tubulointerstitial Fibrosis in Obstructed Kidneys in Hamsters |
| title_full | Contribution of Chymase-Dependent Angiotensin II Formation to the Progression of Tubulointerstitial Fibrosis in Obstructed Kidneys in Hamsters |
| title_fullStr | Contribution of Chymase-Dependent Angiotensin II Formation to the Progression of Tubulointerstitial Fibrosis in Obstructed Kidneys in Hamsters |
| title_full_unstemmed | Contribution of Chymase-Dependent Angiotensin II Formation to the Progression of Tubulointerstitial Fibrosis in Obstructed Kidneys in Hamsters |
| title_short | Contribution of Chymase-Dependent Angiotensin II Formation to the Progression of Tubulointerstitial Fibrosis in Obstructed Kidneys in Hamsters |
| title_sort | contribution of chymase dependent angiotensin ii formation to the progression of tubulointerstitial fibrosis in obstructed kidneys in hamsters |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319311363 |
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