Despite similar reduction of blood pressure and renal ANG II and ET-1 levels aliskiren but not losartan normalizes albuminuria in hypertensive Ren-2 rats.
The relationship between angiotensin II (ANG II) and endothelin-1 (ET-1) is known to be complex; both peptides can initiate and potentiate the gene expression of each other. This pilot study investigated the effects of the AT(1) receptor blocker losartan or the direct renin inhibitor aliskiren on mean arterial pressure (MAP) and albuminuria and the renal ANG II and ET-1 levels. 3-month-old male Ren-2 transgenic rats (TGR) were treated either with losartan (5 mg kg(-1) day(-1)) or aliskiren (10 mg kg(-1) day(-1)) for 10 weeks. At the end of the experiment, rats were decapitated and cortical and papillary parts of kidneys were separated. Plasma and tissue ANG II levels were measured by RIA and tissue ET-1 concentrations by ELISA. In all four groups of animals ET-1 levels were lowest in renal cortex and more than 100-fold higher in the papilla. Cortical and papillary ET-1 concentrations in untreated TGR significantly exceeded those of control HanSD rats and were significantly depressed by both drugs. In both strains, papillary ANG II concentrations were moderately but significantly higher than cortical ANG II, TGR exhibited higher ANG II levels both in cortex and papilla as compared to control HanSD rats. Aliskiren and losartan at the doses used depressed similarly the levels of ANG II in cortex and papilla and reduced ET-1 significantly in the renal cortex and papilla below control levels in HanSD rats. Albuminuria, which was more than twice as high in TGR as in HanSD rats, was normalized with aliskiren and reduced by 28% with losartan, although MAP was reduced to a similar degree by both drugs. Despite similar reductions of MAP and renal ET-1 and ANG II levels aliskiren appears to be more effective than losartan, at the doses used, in reducing albuminuria in heterozygous hypertensive Ren-2 rats.
Vaňourková
Z
Z
Department of Experimental Hypertension, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Kramer
H J
HJ
Husková
Z
Z
Cervenka
L
L
Vaněčková
I
I
D000419:Albuminuria / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000577:Amides / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D015536:Down-Regulation; D019332:Endothelin-1 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005650:Fumarates / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010865:Pilot Projects; D011863:Radioimmunoassay; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics*; D013997:Time Factors
D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D019332:Endothelin-1; D005650:Fumarates; C473112:Ren2 protein, mouse; D000804:Angiotensin II; C446481:aliskiren; D012083:Renin; D019808:Losartan