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 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 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-Dawley (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.

Our findings indicate that an impairment of the pressure-natriuresis mechanism precedes the development of ANG II-dependent hypertension in Cyp1a1-Ren-2 transgenic rats.

Aims: The present study was performed to evaluate the effects of target disruption of the G-protein-coupled receptor Mas for angiotensin 1–7 [Ang(1–7)] in knockout mice on the course of two-kidney, one-clip (2K1C) Goldblatt hypertension. Methods: Knockout and wild-type mice underwent clipping of one renal artery. Blood pressure (BP) was monitored by radiotelemetry. The mice were either untreated or chronically treated with the superoxide (O₂^–) scavenger tempol (400 mg/l) or the inhibitor of NADPH oxidase apocynin (1 g/l) administered in drinking water. Results: Knockout mice responded to clipping by accelerated increases in BP and the final BP was significantly higher than that in wild-type mice. Chronic treatment with tempol or apocynin elicited similar antihypertensive effects in 2K1C/knockout as in 2K1C/wild-type mice. Acute nitric oxide synthase inhibition caused greater BP increases in 2K1C/wild-type than in 2K1C/knockout mice. Conclusion: Our present findings support the notion that the angiotensin-converting enzyme 2-Ang(1–7)-Mas axis serves as an important endogenous physiological counterbalancing mechanism that partially attenuates the hypertensinogenic actions of the activated renin-angiotensin system. The impairment in this axis may contribute to the deterioration of the course of 2K1C Goldblatt hypertension.

The effects of the human renin inhibitor aliskiren on blood pressure (BP), end-organ damage, proteinuria, and tissue and plasma angiotensin (ANG) II levels in young and adult heterozygous Ren-2 transgenic rats (TGR) were evaluated and compared with the effect of the ANG type 1 (AT1) receptor blocker losartan during treatment and after 12 days after the withdrawal of drug treatments. BP was monitored by telemetry from the age of 32 days on (young rats) and at 100 days (adult rats). Aliskiren (10 mg · kg Ϫ1 · day Ϫ1 in osmotic minipumps) or losartan (5 mg · kg Ϫ1 · day Ϫ1 in drinking water) treatment was applied for 28 days in young rats and for 70 days in adult rats. In young untreated TGR, severe hypertension rapidly evolved. Adult untreated TGR exhibited stable established hypertension. Both aliskiren and losartan fully prevented the development of hypertension and cardiac hypertrophy in young TGR and normalized BP and cardiac hypertrophy in adult TGR. After cessation of aliskiren treatment in both young and adult TGR BP and cardiac hypertrophy were persistently reduced, while after losartan withdrawal BP and cardiac hypertrophy rapidly increased. In adult aliskiren-treated rats proteinuria was significantly reduced compared with losartan (the effect persisting after withdrawal of treatment), and this decrease strongly correlated with normalization of glomerular size in these animals. In conclusion, aliskiren and losartan had similar antihypertensive effects during chronic treatment, but the antihypertensive and organoprotective effects of aliskiren were persistent even after the 12-day washout period. The durable effect on proteinuria can possibly be attributed to the normalization of glomerular morphology. losartan; hypertension; direct renin inhibition; glomerular size; morphometry; washout period; blood pressure ALISKIREN, the first clinically approved direct renin inhibitor (31), is a human-specific renin inhibitor that has been demonstrated as an effective blood pressure (BP)-lowering compound in animal and human studies (4, 19, 26) with substantial antiproteinuric (14, 26, 28) and cardioprotective (30, 36) activity. Aliskiren is generally well tolerated, and in combination with other antihypertensives, especially in diabetic patients, it has beneficial effects on proteinuria (10, 26). Recently, much attention has been devoted to the role of (pro)renin receptor in prevention of end-organ damage (9, 12) in both experimental and clinical studies.Models that harbor an extra human [double transgenic rats (2)] or murine [Ren-2 transgenic rats (22)] renin are suitable models for studying the effect of a human renin inhibitor since aliskiren has preferential affinity for human and mouse renin, while that for rat renin is very low. Ren-2 transgenic rats [TGR; official strain name TGR(mRen2-27)] represent a wellestablished model of ANG II-dependent malignant hypertension.Aliskiren has been shown to have antihypertensive and cardioprotective effects in Ren-2 TGR (37) and, additionally, to have nephroprotective (14)...

Pagetův-Schrötterův syndrom (idiopatická trombóza horní končetiny, námahová trombóza) je v povědomí lékařů méně známou klinickou jednotkou, postihující zpravidla mladé jedince s dramatickým průběhem a významnými dlouhodobými následky při nesprávném zaléčení. Cílem této práce je čtenáře seznámit s danou problematikou, diagnostickým a terapeutickým postupem. Součástí textu je kazuistika pacienta dokumentující výskyt tohoto syndromu v klinické praxi. Klíčová slova: Paget-Schröterův syndrom, idiopatická trombóza horní končetiny, námahová trombóza, syndrom horní hrudní apertury. Paget Schroetter syndrome-clinical case of effort thrombosis Paget Schroetter syndrome (idiopatic thrombosis of upper extremity, exertional thrombosis) is generally rare clinical condition with progressively worsening symptoms, which affects mainly young patients. In cases with delayed diagnostic process and inappropriate treatment, it tends to have long term impact on patients health status. This article is mainly concerned with recomended diagnostic and treatment approaches to Paget Schroertter syndrome. There is a case report included in order to prove a manifestation of the syndrome in clinical practice.