Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade
2007
Аутори
Miloradović, ZoranJerkić, Mirjana
Jovović, Đurđica
Mihailović-Stanojević, Nevena
Grujić-Milanović, Jelica
Stošić, Gordana
Marković-Lipkovski, Jasmina
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Background. Acute renal failure (ARF) is a devastating illness, especially when it occurs in various conditions with impaired nitric oxide (NO) synthesis, such as arterial hypertension, heart failure and some renal diseases. We have directed our investigations to effects of both angiotensin II (AII) and endothelin (ET) receptor blockade associated with mild or strong NO deficiency on haemodynamic, biochemical and morphological parameters in experimental post-ischaemic ARF. Methods. In this study, we used bosentan (dual, ETA/ETB-receptor antagonist), losartan (non-peptide, competitive antagonist of type I AII receptor), and NG-nitro-L-arginine methyl ester (L-NAME), inhibitor of NO synthesis. Experiments were performed in anaesthetized, adult male Wistar rats. The right kidney was removed and the renal ischaemia was performed by clamping the left renal artery for 45 min. Experimental groups received receptor antagonists (bosentan or losartan) or vehicle (saline) in the femoral vein 20 m...in before, during and 20 min after the period of ischaemia. L-NAME was given as i.v. bolus before each antagonist infusion. All parameters were measured 24 h after reperfusion. Results. Our results showed that strong NO blockade overcame effects of both ET and AII receptor blockade in experimental post-ischaemic ARF. In addition, the AII receptor blockade had a harmful effect on this condition, probably due to disturbed autoregulatory renal function. On the other hand, ET and AII receptor blockade in mild NO blockade associated with reperfusion injury, improves the most haemodynamic, biochemical and morphological parameters. Conclusions. We concluded that experimental post-ischaemic ARF is neither AII nor ET mediated in case of strong NO blockade, but, in more realistic conditions of mild NO deficiency, these peptides represent significant players whose receptor blockade expressed relevant therapeutic potential.
Кључне речи:
acute renal ischaemia / angiotensin / endothelin / L-NAME / ratsИзвор:
Nephrology Dialysis Transplantation, 2007, 22, 9, 2476-2484Издавач:
- Oxford Univ Press, Oxford
Финансирање / пројекти:
- Улога биолошки активних молекула у експерименталним моделима кардиоваскуларних обољења (RS-MESTD-MPN2006-2010-145054)
DOI: 10.1093/ndt/gfm213
ISSN: 0931-0509
PubMed: 17545678
WoS: 000250112800013
Scopus: 2-s2.0-34548401310
Институција/група
Institut za medicinska istraživanjaTY - JOUR AU - Miloradović, Zoran AU - Jerkić, Mirjana AU - Jovović, Đurđica AU - Mihailović-Stanojević, Nevena AU - Grujić-Milanović, Jelica AU - Stošić, Gordana AU - Marković-Lipkovski, Jasmina PY - 2007 UR - http://rimi.imi.bg.ac.rs/handle/123456789/162 AB - Background. Acute renal failure (ARF) is a devastating illness, especially when it occurs in various conditions with impaired nitric oxide (NO) synthesis, such as arterial hypertension, heart failure and some renal diseases. We have directed our investigations to effects of both angiotensin II (AII) and endothelin (ET) receptor blockade associated with mild or strong NO deficiency on haemodynamic, biochemical and morphological parameters in experimental post-ischaemic ARF. Methods. In this study, we used bosentan (dual, ETA/ETB-receptor antagonist), losartan (non-peptide, competitive antagonist of type I AII receptor), and NG-nitro-L-arginine methyl ester (L-NAME), inhibitor of NO synthesis. Experiments were performed in anaesthetized, adult male Wistar rats. The right kidney was removed and the renal ischaemia was performed by clamping the left renal artery for 45 min. Experimental groups received receptor antagonists (bosentan or losartan) or vehicle (saline) in the femoral vein 20 min before, during and 20 min after the period of ischaemia. L-NAME was given as i.v. bolus before each antagonist infusion. All parameters were measured 24 h after reperfusion. Results. Our results showed that strong NO blockade overcame effects of both ET and AII receptor blockade in experimental post-ischaemic ARF. In addition, the AII receptor blockade had a harmful effect on this condition, probably due to disturbed autoregulatory renal function. On the other hand, ET and AII receptor blockade in mild NO blockade associated with reperfusion injury, improves the most haemodynamic, biochemical and morphological parameters. Conclusions. We concluded that experimental post-ischaemic ARF is neither AII nor ET mediated in case of strong NO blockade, but, in more realistic conditions of mild NO deficiency, these peptides represent significant players whose receptor blockade expressed relevant therapeutic potential. PB - Oxford Univ Press, Oxford T2 - Nephrology Dialysis Transplantation T1 - Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade EP - 2484 IS - 9 SP - 2476 VL - 22 DO - 10.1093/ndt/gfm213 ER -
@article{ author = "Miloradović, Zoran and Jerkić, Mirjana and Jovović, Đurđica and Mihailović-Stanojević, Nevena and Grujić-Milanović, Jelica and Stošić, Gordana and Marković-Lipkovski, Jasmina", year = "2007", abstract = "Background. Acute renal failure (ARF) is a devastating illness, especially when it occurs in various conditions with impaired nitric oxide (NO) synthesis, such as arterial hypertension, heart failure and some renal diseases. We have directed our investigations to effects of both angiotensin II (AII) and endothelin (ET) receptor blockade associated with mild or strong NO deficiency on haemodynamic, biochemical and morphological parameters in experimental post-ischaemic ARF. Methods. In this study, we used bosentan (dual, ETA/ETB-receptor antagonist), losartan (non-peptide, competitive antagonist of type I AII receptor), and NG-nitro-L-arginine methyl ester (L-NAME), inhibitor of NO synthesis. Experiments were performed in anaesthetized, adult male Wistar rats. The right kidney was removed and the renal ischaemia was performed by clamping the left renal artery for 45 min. Experimental groups received receptor antagonists (bosentan or losartan) or vehicle (saline) in the femoral vein 20 min before, during and 20 min after the period of ischaemia. L-NAME was given as i.v. bolus before each antagonist infusion. All parameters were measured 24 h after reperfusion. Results. Our results showed that strong NO blockade overcame effects of both ET and AII receptor blockade in experimental post-ischaemic ARF. In addition, the AII receptor blockade had a harmful effect on this condition, probably due to disturbed autoregulatory renal function. On the other hand, ET and AII receptor blockade in mild NO blockade associated with reperfusion injury, improves the most haemodynamic, biochemical and morphological parameters. Conclusions. We concluded that experimental post-ischaemic ARF is neither AII nor ET mediated in case of strong NO blockade, but, in more realistic conditions of mild NO deficiency, these peptides represent significant players whose receptor blockade expressed relevant therapeutic potential.", publisher = "Oxford Univ Press, Oxford", journal = "Nephrology Dialysis Transplantation", title = "Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade", pages = "2484-2476", number = "9", volume = "22", doi = "10.1093/ndt/gfm213" }
Miloradović, Z., Jerkić, M., Jovović, Đ., Mihailović-Stanojević, N., Grujić-Milanović, J., Stošić, G.,& Marković-Lipkovski, J.. (2007). Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade. in Nephrology Dialysis Transplantation Oxford Univ Press, Oxford., 22(9), 2476-2484. https://doi.org/10.1093/ndt/gfm213
Miloradović Z, Jerkić M, Jovović Đ, Mihailović-Stanojević N, Grujić-Milanović J, Stošić G, Marković-Lipkovski J. Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade. in Nephrology Dialysis Transplantation. 2007;22(9):2476-2484. doi:10.1093/ndt/gfm213 .
Miloradović, Zoran, Jerkić, Mirjana, Jovović, Đurđica, Mihailović-Stanojević, Nevena, Grujić-Milanović, Jelica, Stošić, Gordana, Marković-Lipkovski, Jasmina, "Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade" in Nephrology Dialysis Transplantation, 22, no. 9 (2007):2476-2484, https://doi.org/10.1093/ndt/gfm213 . .