Carvedilol Protects against Glomerulosclerosis in Rat Remnant Kidney without General Changes in Antioxidant Enzyme Status

Branden, Christiane Van Den; Gabriels, Margriet; Vamecq, Jòseph; Houte, Katherina Vanden; Verbeelen, Dierik

doi:10.1159/000190295

Cited by 23 publications

(16 citation statements)

References 17 publications

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“…There may also be substantial differences between different ␤-blocking drugs. Third-generation ␤-blockers, such as carvedilol and nebivolol, seem to have more protective effects than traditional ␤-blockers, 47,63 possibly via stimulation of NO release. 58 In fact, carvedilol is even protective in acute renal failure after gentamicin.…”

Section: ␤-Adrenergic Receptor Blockadementioning

confidence: 99%

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Causes and Consequences of Increased Sympathetic Activity in Renal Disease

2004

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Abstract-Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only caused by hypertension. Another characteristic of renal disease is unbalanced nitric oxide (NO) and angiotensin (Ang) activity. Increased SNA in renal disease may be sustained because a state of NO-Ang II unbalance is also present in the hypothalamus. Very few studies have directly compared the efficacy of adrenergic blockade with other renoprotective measures. Third-generation ␤-blockers seem to have more protective effects than traditional ␤-blockers, possibly via stimulation of NO release. Although it has been extensively documented that muscle SNA is increased in chronic renal failure, data on renal SNA and cardiac SNA are not available for these patients before end-stage renal disease. It is also unknown whether additional treatment with third-generation ␤-blockers can delay the progression of renal injury and prevent cardiac injury in chronic renal failure more efficiently than conventional treatment with angiotensin-converting enzyme inhibitors only. Key Words: renal disease Ⅲ antihypertensive agents Ⅲ hypertension Ⅲ diabetic nephropathy Ⅲ sympathetic nervous system I t is well known that irrespective of the primary cause of renal injury, chronic renal disease often leads to renal fibrosis and end-stage renal disease (ESRD). Delaying the onset of renal replacement therapy is of utmost importance, both medically and economically. 1 Many quite different interventions (dietary protein or phosphate restriction, inhibition of the renin-angiotensin system [RAS], endothelin receptor antagonists, aldosterone antagonists, antioxidants, renal denervation, HMG-CoA reductase inhibitors, etc) have been shown to considerably slow this process in experimental models. In fact, if these were all discrete pathways, then combining such interventions would provide additive protective effects that would exceed the loss of function. Clearly, this is not the case, suggesting that parallel extracellular pathways converge on common intracellular signaling molecules, which in turn activate a limited number of transcription factors that turn on excessive matrix synthesis. Recent studies using modulation of intracellular signaling pathways, eg, by gene transfer of Smad 7, 2 or inhibition of transcription factors with antisense technology 3 show marked reduction of fibrosis in robust models such as unilateral ureteral obstruction. Another pathway that is gaining increasing attention is the independent role of proteinuria in causing interstitial inflammation and ultimately fibrosis. 4 Such inflammation causes cytokine release and consequent monocyte influx. Preventing this monocyte influx by anti-monocyte chemoattractant protein (MCP)-1 gene therapy 5 also reduces injury.In the clinical setting, however, the intracellular domain i...

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Section: ␤-Adrenergic Receptor Blockadementioning

confidence: 99%

“…40,[62][63][64][65] Renal protection by ␤-blockade has also been observed in NOS inhibition 66 -68 and in stroke-prone SHR on high-salt intake. 47 Experimental studies of renal injury that evaluated adrenergic blockade are listed in Table 1.…”

Section: ␤-Adrenergic Receptor Blockadementioning

confidence: 99%

Causes and Consequences of Increased Sympathetic Activity in Renal Disease

2004

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“…When studied, the efficacy was comparable to that of interference with the RAS (52, 82, 90) or with a calcium antagonist (94). Both ␣-adrenergic blockade (51, 85,87,88,90,91) and ␤-adrenergic blockade (51, 80,83,84,92,93) have protective action, and summation of their effects occurs (51). In a model of type 2 diabetes, combining adrenergic blockade with RAS blockade offered only slightly better protection (90), which may not be surprising because there is probably much overlap in downstream pathways leading to renal damage.…”

Section: Sympathetic Hyperactivity and Kidney Damagementioning

confidence: 99%

“…Nonetheless, attenuation of progression of renal failure by inhibition of sympathetic action, by either renal denervation or pharmacologic agents, has been found in diverse rat models of CRF, such as subtotal nephrectomy by surgical excision (52, 80), or by infarction (81)(82)(83)(84), NOS inhibition (85-88), streptozotocininduced diabetes (89), and type 2 diabetes in corpulent SHR (90,91) and in salt-loaded stroke-prone SHR (92,93). When studied, the efficacy was comparable to that of interference with the RAS (52, 82, 90) or with a calcium antagonist (94).…”

Section: Sympathetic Hyperactivity and Kidney Damagementioning

confidence: 99%

Sympathetic Hyperactivity in Chronic Renal Failure

Koomans

Blankestijn

Joles

2004

Journal of the American Society of Nephrology

185

145

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Abstract. Sympathetic hyperactivity plays an important and distinct role in hypertension associated with chronic renal failure (CRF). Renal ischemia, elevated angiotensin II, and suppressed brain nitric oxide (NO) all stimulate sympathetic activity. Evidence is accumulating for a role of sympathetic hyperactivity in renal and cardiac damage in patients with CRF. Decreased NO availability and increased oxidative stress, characteristic in CRF patients, seem to sensitize target organs for damaging actions of sympathetic hyperactivity. Fortunately, sympatholytic agents can slow down progression of renal and cardiac dysfunction. Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists suppress sympathetic activity, but complete elimination of the effect of sympathetic hyperactivity can be obtained only with specific adrenergic blockers. However, this important therapeutic option is grossly neglected, painfully illustrated by the unwillingness to treat CRF patients with ␤-blockers, even if they have had a myocardial infarction. After discussion of mechanisms and effects of the sympathetic hyperactivity, a case is made for increased application of specific adrenergic blockers in patients with CRF.Hypertension remains an important issue in patients with chronic renal failure (CRF). It plays a key role in progression of renal failure and forms the basis for the cardiovascular complications and mortality. Although this point is widely recognized, BP control in patients with CRF, whether in an early or advanced stage or when on dialysis, is often poor (1, 2).Hypervolemia and activated renin angiotensin system (RAS) have long been acknowledged as major determinants of hypertension in CRF, and in most patients, both need to be controlled to normalize BP. Besides, it has been shown in several trials that the renoprotective effect of RAS suppression extends beyond BP lowering only. This applies particularly to patients with diabetic (3-6) or nondiabetic (3, 5, 7) glomerulopathy.It has also become clear that many other factors cause renal hypertension. These include elevated levels of endothelin, sympathetic activity, and oxidant stress and reduced levels of NO and medullary vasodilating factors (8 -10). As is the case for angiotensin II, many of these factors probably damage the kidney and the cardiovascular system independent of their hypertensive effect. However, as long as their pathogenic role has not been proved in large clinical trials, it is understandable that these factors are still regarded as foot-soldiers compared with the well-accepted nobility of volume and RAS-understandable, but probably not right. Already several Cinderellas have been identified that relate CRF to cardiovascular disease, i.e., the underestimated role of renal dysfunction in cardiovascular risk profile (11) and of cardiac systolic dysfunction in dialysis patients (12). We can do without one more. In this review, we highlight the pathogenesis of sympathetic hyperactivity in CRF and the evidence for its role in organ damage...

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“…Experimental studies showed that carvedilol can reduce focal sclerosis, lipid peroxidation, and serum urea and creatinine levels. [21] Various hypotheses could be advanced to explain this effect of carvedilol. Unlike conventional beta blockers, carvedilol does not reduce glomerular filtration rate, effective renal plasma flow, blood urea nitrogen, or serum creatinine, and significantly decreases renal vascular resistance.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Higher Dose of Losartan Treatment with Losartan Plus Carvedilol and Losartan Plus Ramipril in Patients with Glomerulonephritis and Proteinuria

et al. 2007

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Background. Proteinuria may cause a worsening of accompanying renal disease or even lead to glomerulosclerosis. There is no data about the effect of carvedilol on patients with proteinuric (>0.5 g/day) glomerulonephritis. This study aimed to compare the effects of carvedilol with ramipril and losartan in patients with proteinuric glomerulonephritis. Methods. Twenty-one glomerulonephritis patients were followed for 12 months. Patients were divided into three groups. All patients were treated with losartan 50 mg once daily for two weeks. After two weeks (baseline), patients were given additional medications: 50 mg losartan, 5 mg ramipril, and 25 mg carvedilol were given additionally to the patients in groups 1, 2, and 3 respectively. Results. Baseline mean proteinuria values of patients in groups 1, 2 and 3 were 1.6 ± 1.1 g/day, 2.1 ± 1.3 g/ day, and 1.4 ± 1.2 g/day, respectively. These values decreased to 0.5 ± 0.7 g/day, 0.6 ± 0.7 g/day, and 0.9 ± 0.9 g/day, respectively, at the end of the 12 th month. These results were statistically significant only in group 1 (p = 0.04). The rational variation of proteinuria between the first and 12 th month of losartan, ramipril, and carvedilol were −61%, −62%, and −27%, respectively. The decreases in blood pressures between baseline and the first, sixth, and twelfth-month measurements were significant in all groups. Conclusions. Thee results showed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (AT1ras) provide marked decreases in proteinuria, making their use indisputable in patients with glomerulonephritis. Carvedilol was not found to be as effective as ACEIs and AT1ras in decreasing proteinuria and preserving renal function.

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Carvedilol Protects against Glomerulosclerosis in Rat Remnant Kidney without General Changes in Antioxidant Enzyme Status

Cited by 23 publications

References 17 publications

Causes and Consequences of Increased Sympathetic Activity in Renal Disease

Causes and Consequences of Increased Sympathetic Activity in Renal Disease

Sympathetic Hyperactivity in Chronic Renal Failure

Comparison of Higher Dose of Losartan Treatment with Losartan Plus Carvedilol and Losartan Plus Ramipril in Patients with Glomerulonephritis and Proteinuria

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