Tacrolimus-induced hypertension and nephrotoxicity in Fawn-Hooded rats are attenuated by dual inhibition of renin-angiotensin system
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24718302
DOI
10.1038/hr.2014.79
PII: hr201479
Knihovny.cz E-resources
- MeSH
- Acute Kidney Injury chemically induced prevention & control MeSH
- Adrenergic beta-Antagonists pharmacology MeSH
- Calcium Channel Blockers pharmacology MeSH
- Angiotensin II Type 1 Receptor Blockers pharmacology MeSH
- Diet MeSH
- Immunosuppressive Agents antagonists & inhibitors toxicity MeSH
- Angiotensin-Converting Enzyme Inhibitors pharmacology MeSH
- Calcineurin drug effects MeSH
- Rats MeSH
- Renin-Angiotensin System drug effects MeSH
- Tacrolimus antagonists & inhibitors toxicity MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adrenergic beta-Antagonists MeSH
- Calcium Channel Blockers MeSH
- Angiotensin II Type 1 Receptor Blockers MeSH
- Immunosuppressive Agents MeSH
- Angiotensin-Converting Enzyme Inhibitors MeSH
- Calcineurin MeSH
- Tacrolimus MeSH
Chronic immunosuppressive therapy is often complicated by the development of both arterial hypertension and renal dysfunction. The principal aim of this study was to assess the effects of dual inhibition of renin-angiotensin system (RAS) and other antihypertensive treatment on blood pressure and renal function in normotensive and hypertensive Fawn-Hooded (FH) strains during chronic calcineurin inhibitor (CNI) administration. Combinations of perindopril (5 mg kg(-1) per day) and losartan (50 mg kg(-1) per day) or amlodipine (6 mg kg(-1) per day) and metoprolol (80 mg kg(-1) per day) were administered to normotensive (FHL) and hypertensive (FHH) rats, fed with diet containing tacrolimus (Tac; 12 mg kg(-1) per day). Tac-induced arterial hypertension in both animal strains (FHL: 151±4; FHH: 198±6 mm Hg) was prevented by dual RAS inhibition (FHL: 132±3 mm Hg, P<0.05; FHH: 153±3 mm Hg, P<0.05) as well as by a combination of amlodipine and metoprolol (FHL: 136±3 mm Hg, P<0.05; FHH: 166±4 mm Hg, P<0.05). However, significant nephroprotection was observed only in animals on dual RAS inhibition where albuminuria was reduced in both FHL (51.1±3.9 vs. 68.3±4.5 μg per day; P<0.05) and FHH rats (13.1±0.3 vs. 18.8±0.7 mg per day; P<0.05). We also found Tac-induced enhancement in renal angiotensin II activity that was significantly reduced by dual RAS inhibition in both FHL (63.5±3.2 vs. 23.1±3.0 fmol g(-1)) and FHH (79.8±8.5 vs. 32.2±5.8 fmol g(-1)). In addition, histological analysis revealed that RAS inhibition noticeably diminished glomerulosclerosis and tubulo-interstitial injury. This study indicates that dual blockade of RAS significantly attenuates Tac-induced arterial hypertension and nephrotoxicity in FH rats and further supports the notion that RAS inhibitors display efficient renoprotective properties during CNI treatment.
Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic
Department of Clinical Pharmacology University Medical Center Groningen Groningen The Netherlands
References provided by Crossref.org
