Impairment of the autoregulation of renal hemodynamics and of the pressure-natriuresis relationship precedes the development of hypertension in Cyp1a1-Ren-2 transgenic rats

Erbanová, Michaela; Thumová, Monika; Husková, Zuzana; Vaněčková, Ivana; Vaňourková, Zdeňka; Mullins, John J.; Kramer, Herbert J.; Bürgelová, Marcela; Rakušan, Dan; Červenka, Luděk

doi:10.1097/hjh.0b013e32831cbd5a

Cited by 23 publications

(27 citation statements)

References 34 publications

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“…aÀENaC subunit mRNA abundance in small intrarenal arteries remained unaltered after 3 weeks of transgene induction even in the face of very high plasma renin and aldosterone concentrations during amiloride treatment. Using AT 1 receptor blockade with losartan, known to effectively lower arterial pressure in cyp1a1ren-2 transgenic rats [14,15], as a reference, we tested the efficacy of ENaC blockade with amiloride or mineralocorticoid receptor blockade with spironolactone to lower arterial pressure in these rats. While amiloride was as effective as losartan in lowering arterial pressure in transgeneinduced cyp1a1ren-2 transgenic rats, spironolactone had no effect.…”

Section: Discussionmentioning

confidence: 99%

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Amiloride lowers arterial pressure in cyp1a1ren-2 transgenic rats without affecting renal vascular function

Schlüter

Rohsius

Wanka

et al. 2010

Journal of Hypertension

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Section: Discussionmentioning

confidence: 99%

“…The severity of the hypertensive phenotype can be determined by varying the dose of I3C [13,14]. Increased renal vascular resistance is an early event during the development of hypertension in these rats [15].…”

Section: Introductionmentioning

confidence: 99%

Amiloride lowers arterial pressure in cyp1a1ren-2 transgenic rats without affecting renal vascular function

Schlüter

Rohsius

Wanka

et al. 2010

Journal of Hypertension

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“…To study renal autoregulation, a previously described protocol was employed (9,46). Briefly, rats were anesthetized with thiopental (50 mg/kg ip) and placed on a thermoregulated surgical table to maintain body temperature at 37 0 C. A tracheotomy was performed, and a PE-240 tube was inserted to maintain a patent airway.…”

Section: Methodsmentioning

confidence: 99%

Role of cytochromeP-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats

Sporková

Kopkan

Varcabová

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Alterations in renal function contribute to Goldblatt two-kidney, one-clip (2K1C) hypertension. A previous study indicated that bioavailability of cytochrome P-450 metabolites epoxyeicosatrienoic acids (EETs) is decreased while that of 20-hydroxyeicosatetraenoic acids (20-HETE) is increased in this model. We utilized the inhibitor of soluble epoxide hydrolase cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB) and HET-0016, the inhibitor of 20-HETE production, to study the role of EETs and 20-HETE in the regulation of renal function. Chronic c-AUCB treatment significantly decreased systolic blood pressure (SBP) (133 ± 1 vs. 163 ± 3 mmHg) and increased sodium excretion (1.23 ± 0.10 vs. 0.59 ± 0.03 mmol/day) in 2K1C rats. HET-0016 did not affect SBP and sodium excretion. In acute experiments, renal blood flow (RBF) was decreased in 2K1C rats (5.0 ± 0.2 vs. 6.9 ± 0.2 ml·min(-1)·g(-1)). c-AUCB normalized RBF in 2K1C rats (6.5 ± 0.6 ml·min(-1)·g(-1)). HET-0016 also increased RBF in 2K1C rats (5.8 ± 0.2 ml·min(-1)·g(-1)). Although RBF and glomerular filtration rate (GFR) remained stable in normotensive rats during renal arterial pressure (RAP) reductions, both were significantly reduced at 100 mmHg RAP in 2K1C rats. c-AUCB did not improve autoregulation but increased RBF at all RAPs and shifted the pressure-natriuresis curve to the left. HET-0016-treated 2K1C rats exhibited impaired autoregulation of RBF and GFR. Our data indicate that c-AUCB displays antihypertensive properties in 2K1C hypertension that are mediated by an improvement of RBF and pressure natriuresis. While HET-0016 enhanced RBF, its anti-natriuretic effect likely prevented it from producing a blood pressure-lowering effect in the 2K1C model.

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“…26 In addition, this standardized approach allowed us to compare the present results with those from our previous studies; this helped evaluate the role of the RAS in the pathophysiology of hypertension on the basis of our long-term research. 26,27,[36][37][38][39][40] Urinary aldosterone concentrations were measured by a commercially available RIA kit (Immunotech, Prague, Czech Republic) as described previously. 40 Plasma and urinary creatinine concentrations were measured by the picric acid colorimetric method using a commercially available kit (Lachema, Brno, Czech Republic).…”

Section: Therapeutic Regimesmentioning

confidence: 99%

Similar renoprotection after renin‐angiotensin‐dependent and ‐independent antihypertensive therapy in 5/6‐nephrectomized Ren‐2 transgenic rats: are there blood pressure‐independent effects?

Kujal

Chábová

Vernerová³

et al. 2010

Clin Exp Pharma Physio

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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.

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Impairment of the autoregulation of renal hemodynamics and of the pressure-natriuresis relationship precedes the development of hypertension in Cyp1a1-Ren-2 transgenic rats

Abstract: 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.

Cited by 23 publications

References 34 publications

Amiloride lowers arterial pressure in cyp1a1ren-2 transgenic rats without affecting renal vascular function

Amiloride lowers arterial pressure in cyp1a1ren-2 transgenic rats without affecting renal vascular function

Role of cytochromeP-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats

Similar renoprotection after renin‐angiotensin‐dependent and ‐independent antihypertensive therapy in 5/6‐nephrectomized Ren‐2 transgenic rats: are there blood pressure‐independent effects?

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