title: Effects of combined endothelin A receptor and renin-angiotensin system blockade on the course of end-organ damage in 5/6 nephrectomized Ren-2 hypertensive rats.
abstract: Our previous studies in rats with ablation nephrectomy have shown similar cardiorenal protective effects of renin-angiotensin system (RAS)-dependent treatment (combination of angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker) and RAS-independent treatment (combination of α- and β-adrenoreceptor antagonist and diuretics). Moreover, selective blockade of endothelin (ET) receptor type A (ET(A)) improved survival rate and attenuated hypertension and organ damage in Ren-2 transgenic rats. Therefore, we were interested in whether ET(A) receptor blockade could have additive effects to the classical blockade of the RAS. Transgenic rats underwent 5/6 renal ablation at the age of 2 months and were treated for 20 weeks with RAS blockers alone (angiotensin II receptor blocker - losartan, and angiotensin-converting enzyme inhibitor - trandolapril), ET(A) receptor blocker alone (atrasentan) or with the combination of RAS and ET(A) receptor blockade. RAS blockade normalized blood pressure and improved survival. It decreased cardiac hypertrophy and proteinuria as well as tissue angiotensin II and ET-1 levels. In contrast, ET(A) receptor blockade only partially improved survival rate, reduced blood pressure, attenuated the development of cardiac hypertrophy and transiently reduced proteinuria. However, no additive cardio- and renoprotective effects of ET(A) and RAS blockade were noted at the end of the study.
authors.affiliation: Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic. ivanava@biomed.cas.cz
authors.forename: Ivana
authors.initials: I
authors.lastname: Vaněčková
authors.forename: Petr
authors.initials: P
authors.lastname: Kujal
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Husková
authors.forename: Zdeňka
authors.initials: Z
authors.lastname: Vaňourková
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Vernerová
authors.forename: Věra
authors.initials: V
authors.lastname: Certíková Chábová
authors.forename: Petra
authors.initials: P
authors.lastname: Skaroupková
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Kramer
authors.forename: Vladimír
authors.initials: V
authors.lastname: Tesař
authors.forename: Luděk
authors.initials: L
authors.lastname: Červenka
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000077868:Atrasentan; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D065130:Endothelin A Receptor Antagonists; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009392:Nephrectomy / Q000379:methods; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D065130:Endothelin A Receptor Antagonists; D007211:Indoles; D011759:Pyrrolidines; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A; C052035:trandolapril; D019808:Losartan; D000077868:Atrasentan