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This may lead to identification of new therapeutic targets to reduce the development of heart failure after MI. Readers are invited to give their opinion on this article. To submit a comment, go to: http://ep.physoc.org/letters/submit/expphysiol;98/3/606 Research in the laboratory of G.A.G. is supported by the British Heart Foundation, the Wellcome Trust and the British Heart Foundation Centre for Research Excellence. Helen Jeanes, Gavin Merrifield and Sara McSweeney assisted with data collection. ""1. Hypertension plays a critical role in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD), but it has also been postulated that antihypertensive [http://www.selleckchem.com/products/ch5424802.html see more] drugs that block the renin-angiotensin system (RAS) show class-specific renoprotective actions beyond their blood pressure (BP)-lowering effects. 2. Because this notion has recently been questioned, in the present study we compared the effects of a RAS-dependent antihypertensive therapy (a combination of trandolapril, an angiotensin-converting enzyme inhibitor (ACEI) and losartan, an angiotensin-II (AngII) receptor subtype 1A receptor [http://www.selleckchem.com/products/azd9291.html Selleck Osimertinib] antagonist) with a ��RAS-independent�� antihypertensive therapy (a combination of labetalol, an alfa- and beta-adrenoreceptor antagonist with the diuretics, hydrochlorothiazide and furosemide) on the progression of CKD after 5/6 renal ablation (5/6 NX) in Ren-2 renin transgenic rats (TGR), a model of AngII-dependent hypertension. Normotensive transgene-negative Hannover Sprague�CDawley (HanSD) rats after 5/6 NX served as controls. 3. RAS-dependent and -independent antihypertensive therapies normalized BP and survival rate, and prevented the development of cardiac hypertrophy and glomerulosclerosis to the same degree in 5/6 NX HanSD rats and in 5/6 NX TGR. The present findings show that renoprotection, at least in rats after 5/6 NX, is predominantly BP-dependent. When equal lowering of BP was achieved, leading to normotension, cardio- and renoprotective effects were equivalent irrespective of the type of antihypertensive therapy. 4. These findings should be taken into consideration in attempts to develop new therapeutic approaches and strategies aimed to prevent the progression of CKD and to lower the incidence of ESRD. ""What is the central question of this study? Based [http://en.wikipedia.org/wiki/GPX4 GPX4] on the relevance of the renin�Cangiotensin system and the controversy regarding the role of the sympathetic nervous system in thyroid hormone-related cardiac hypertrophy, the present study sought to establish whether there is a gender difference in activation of these systems and the degree of cardiac hypertrophy in mice. What is the main finding and its importance? Triiodothyronine increased sympathetic modulation and induced higher levels of cardiac angiotensin?II in male than in female mice.