The cellular mechanisms involved in the vasodilator effect of nebivolol on the renal artery

Georgescu, Adelina; Pluteanu, Florentina; Flonta, Maria-Luiza; Bădilă, Elisabeta; Dorobanțu, Maria; Popov, Doina

doi:10.1016/j.ejphar.2004.11.043

Cited by 58 publications

(69 citation statements)

References 24 publications

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“…There have been very limited studies exploring the effects of nebivolol treatment in states of proteinuria and glomerular injury. Our novel work extends previous limited work with this unique beta-blocker as it relates to renal tissue levels of bioavailable NO and reductions in renal disease [8, 10, 12, 13]. …”

Section: Discussionsupporting

confidence: 57%

“…Additionally, nebivolol therapy promotes endothelium-dependent vasodilation through the L -arginine/NO pathway in different regional vascular beds [14, 15]. Limited studies have shown that systemic treatment with this beta-blocker increases renal tissue levels of bioavailable NO and reduces renal fibrosis [8, 10, 12, 13]. However, there have been very limited studies exploring the impact of nebivolol treatment on the kidney in animal models displaying glomerular injury and proteinuria.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, NO appears to counter-regulate the effects of both the SNS and RAAS in the renal regulation of salt and fluid homeostasis as well as renal injury [6, 7]. Indeed, treatment strategies to increase bioavailable NO have been shown to protect against renal damage in several rodent models of RAAS and SNS-mediated renal sclerosis [9,10,11,12,13]. In this context, beta-blockers are known to suppress both the SNS and RAAS [14,15,16,17,18,19].…”

Section: Introductionmentioning

confidence: 99%

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Nebivolol Reduces Proteinuria and Renal NADPH Oxidase-Generated Reactive Oxygen Species in the Transgenic Ren2 Rat

Whaley‐Connell

Habibi²,

Johnson³

et al. 2009

Am J Nephrol

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Background/Aims: Renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system activation are crucial in the pathogenesis of hypertension, cardiovascular and renal disease. NADPH oxidase-mediated increases in reactive oxygen species (ROS) are an important mediator for RAAS-induced cardiovascular and renal injury. Increased levels of ROS can diminish the bioactivity of nitric oxide (NO), a critical modulator of RAAS effects on the kidney. Thereby, we hypothesized that in vivo nebivolol therapy in a rodent model of activated RAAS would attenuate glomerular damage and proteinuria through its actions to reduce NADPH oxidase activity/ROS and increase bioavailable NO. Methods: We utilized the transgenic Ren2 rat which displays heightened tissue RAAS, hypertension, and proteinuria. Ren2 rats (6–9 weeks of age) and age-matched Sprague-Dawley littermates were treated with nebivolol 10 mg/kg/day (osmotic mini-pump) for 21 days. Results: Ren2 rats exhibited increases in systolic blood pressure, proteinuria, kidney cortical tissue total NADPH oxidase activity and subunits (Rac1, p67^phox, and p47^phox), ROS and 3-nitrotyrosine, as well as reductions in podocyte protein markers; each of these parameters improved with nebivolol treatment along with increases in renal endothelial NO synthase expression. Conclusions: Our data suggest that nebivolol improves proteinuria through reductions in renal RAAS-mediated increases in NADPH oxidase/ROS and increases in bioavailable NO.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nebivolol Reduces Proteinuria and Renal NADPH Oxidase-Generated Reactive Oxygen Species in the Transgenic Ren2 Rat

Whaley‐Connell

Habibi²,

Johnson³

et al. 2009

Am J Nephrol

View full text Add to dashboard Cite

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“…Our findings suggest that nebivolol may potentiate the beneficial effects of angioplasty, but these effects appear not to be obviously related to NO-dependent mechanisms [20]. It has been shown by others also, that nebivolol may influence the renal circulation by non-NO-mediated mechanisms [20] that clearly deserve further study in human hypertension.…”

Section: Discussionmentioning

confidence: 99%

Nebivolol Improves Renal Function in Patients Who Underwent Angioplasty due to Renal Artery Stenosis: A Pilot Study

Duranay¹,

Kanbay²,

Akay³

et al. 2009

Nephron Clin Pract

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Renal artery stenosis (RAS) is a progressive disease and may lead to chronic kidney disease by deterioration of renal functions. Endothelial dysfunction is an important causative factor for kidney damage after RAS revascularization. Nebivolol, a new generation beta blocker induces endothelium-related arterial relaxation by nitric oxide (NO) and may improve endothelial dysfunction. This pilot study tested the effect of nebivolol on the glomerular filtration rate (GFR) in a series of 33 patients with severe RAS (>70%) who underwent revascularization. After revascularization, nebivolol was added to antihypertensive treatment in 17 randomly selected patients while 16 patients (control group) continued their standard treatment. Estimated glomerular filtration rate (eGFR), proteinuria as well as nitrite and nitrate levels were measured at baseline and 6 months after the revascularization procedure. Six months after revascularization, eGFR increased from 44.8 to 50.6 ml/min in the nebivolol group. In contrast, eGFR did not change in the control group. Nitrite/nitrate levels decreased to a significant extent both in the nebivolol and in the control group. Proteinuria decreased more in the nebivolol group compared to the control group. These pilot data support a full-fledged clinical trial, testing whether nebivolol may be beneficial in the post-revascularization phase in patients with RAS.

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“…Currently, there are limited studies exploring the impact of nebivolol treatment on the kidney in animal models displaying tubulointerstitial injury [39,40,41,42]. Recently, we observed that nebivolol treatment in Ren2 rats reduced proteinuria, and increased the podocyte-specific markers podocin and desmin [34].…”

Section: Introductionmentioning

confidence: 99%

Nebivolol Attenuates Maladaptive Proximal Tubule Remodeling in Transgenic Rats

Hayden

Habibi²,

Whaley‐Connell³

et al. 2010

Am J Nephrol

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Background/Aims: The impact of nebivolol therapy on the renal proximal tubular cell (PTC) structure and function was investigated in a transgenic (TG) rodent model of hypertension and the cardiometabolic syndrome. The TG Ren2 rat develops nephropathy with proteinuria, increased renal angiotensin II levels and oxidative stress, and PTC remodeling. Nebivolol, a β₁-antagonist, has recently been shown to reduce albuminuria, in part, through reductions in renal oxidative stress. Accordingly, we hypothesized that nebivolol therapy would attenuate PTC damage and tubulointerstitial fibrosis. Methods: Young Ren2 (R2-N) and SD (SD-N) rats were treated with nebivolol (10 mg/kg/day) or vehicle (R2-C; SD-C) for 3 weeks. PTC structure and function were tested using transmission electron microscopy and functional measurements. Results: Nebivolol treatment decreased urinary N-acetyl-β-D-glucosaminidase, tubulointerstitial ultrastructural remodeling and fibrosis, NADPH oxidase activity, 3-nitrotyrosine levels, and increased megalin and lysosomal-associated membrane protein-2 immunostaining in PTCs. Ultrastructural abnormalities that were improved with therapy included altered canalicular structure, reduced endosomes/lysosomes and PTC vacuoles, basement membrane thickening, and mitochondrial remodeling/fragmentation. Conclusion: These observations support the notion that nebivolol may improve PTC reabsorption of albumin and other glomerular filtered small molecular weight proteins in association with the attenuation of oxidative stress, tubulointerstitial injury and fibrosis in this rat model of metabolic kidney disease.

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The cellular mechanisms involved in the vasodilator effect of nebivolol on the renal artery

Cited by 58 publications

References 24 publications

Nebivolol Reduces Proteinuria and Renal NADPH Oxidase-Generated Reactive Oxygen Species in the Transgenic Ren2 Rat

Nebivolol Reduces Proteinuria and Renal NADPH Oxidase-Generated Reactive Oxygen Species in the Transgenic Ren2 Rat

Nebivolol Improves Renal Function in Patients Who Underwent Angioplasty due to Renal Artery Stenosis: A Pilot Study

Nebivolol Attenuates Maladaptive Proximal Tubule Remodeling in Transgenic Rats

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