Impact of renal transplantation on small vessel reactivity1

Gabriëls, Gert; August, Christian; Grisk, Olaf; Steinmetz, Martin; Kosch, Markus; Rahn, K. H.; Schlatter, Eberhard

doi:10.1097/01.tp.0000044111.12370.ed

Cited by 31 publications

(22 citation statements)

References 29 publications

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“…Besides mesenteric resistance arteries, renal resistance arteries may also be affected and this may in part contribute to CsA-induced nephrotoxicity and renal vasculopathy. However, our results are to some degree inconsistent with findings that postulated that resistance vessels obtained from transplanted kidneys were more sensitive to NE [27]. The findings of a decreased sensitivity to noradrenaline are in contrast to previous reports of an enhanced vascular sensitivity to adrenergic agonists in the presence of CsA: intramuscular administration of surplus doses of CsA (20 mg/kg/day) for 7 days enhanced vasoconstriction in response to noradrenaline [28].…”

Section: Discussioncontrasting

confidence: 57%

Cyclosporine A Impairs Norepinephrine-Induced Vascular Contractility

Bergler

Resch

Reinhold

et al. 2012

Kidney Blood Press Res

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Usage of cyclosporine A (CsA) after kidney transplantation may be associated with development of nephrotoxicity and vasculopathy, but the mechanisms by which CsA causes vascular dysfunction are still under scrutiny. We established a transplantation model and investigated the effect of CsA on vascular contractility with the aid of a pressurized myograph in comparison with control and unilaterally nephrectomized rats. Results were correlated with mRNA expression studies of α- and β-adrenoreceptors, in mesenteric resistance arteries versus the thoracic aorta. Consequences of everolimus on functional properties as well as adrenoreceptor expression were also studied. CsA significantly downregulated expression of mesenteric adrenoreceptors, whereas no effect on aortic adrenoreceptors was seen. Administration of everolimus had no influence on mRNA adrenoreceptor expression in mesenteric resistance arteries. Furthermore, contractile responses of mesenteric resistance arteries to norepinephrine were markedly reduced after treatment with CsA, while there was no difference in contraction by endothelin. Everolimus did not alter the contractility response at all. In summary, norepinephrine-induced, but not endothelin-induced, contractile responses of mesenteric resistance arteries are blunted in CsA-treated rats. This finding was accompanied by a marked downregulation of adrenoreceptors in mesenteric resistance arteries and was limited to the usage of CsA.

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Section: Discussioncontrasting

confidence: 57%

Cyclosporine A Impairs Norepinephrine-Induced Vascular Contractility

Bergler

Resch

Reinhold

et al. 2012

Kidney Blood Press Res

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“…Similarly, sympathetic denervation in transplanted kidneys results in a significant decrease in local norepinephrine concentrations (28), with a potential effect on intrarenal oxygen bioavailability. However, experimental studies suggest that the medullary blood flow may be insensitive to sympathetic nerve activity (25) and that changes in renal vascular resistance are not explained by denervation (27). As far as CNI use and oxygen bioavailability are concerned, we have been unable to show a correlation between the dose and/or the blood level of CNIs and MR2* or CR2* values in both acute (20) and chronic allograft dysfunction (current study, data not shown).…”

Section: Discussionmentioning

confidence: 66%

BOLD-MRI assessment of intrarenal oxygenation and oxidative stress in patients with chronic kidney allograft dysfunction

Djamali¹,

Sadowski²,

Muehrer³

et al. 2007

American Journal of Physiology-Renal Physiology

111

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Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) uses deoxyhemoglobin as an endogenous contrast agent for the noninvasive assessment of tissue oxygen bioavailability. We hypothesized that intrarenal oxygenation was impaired in patients with chronic allograft nephropathy (CAN). Ten kidney-transplant recipients with CAN and nine healthy volunteers underwent BOLD-MRI. Medullary R2* (MR2*) and cortical R2* (CR2*) levels (measures directly proportional to tissue deoxyhemoglobin levels) were determined alongside urine and serum markers of oxidative stress (OS): hydrogen peroxide (H(2)O(2)), F(2)-isoprostanes, total nitric oxide (NO), heat shock protein 27 (HSP27), and total antioxidant property (TAOP). Mean MR2* and CR2* levels were significantly decreased in CAN (increased local oxyhemoglobin concentration) compared with healthy volunteers (20.7 +/- 1.6 vs. 23.1 +/- 1.8/s, P = 0.03 and 15.9 +/- 1.9 vs. 13.6 +/- 2.3/s, P = 0.05, respectively). There was a significant increase in serum and urine levels of H(2)O(2) and serum HSP27 levels in patients with CAN. Conversely, urine NO levels and TAOP were significantly increased in healthy volunteers. Multiple linear regression analyses showed a significant association between MR2* and CR2* levels and serum/urine biomarkers of OS. BOLD-MRI demonstrated significant changes in medullary and cortical oxygen bioavailability in allografts with CAN. These correlated with serum/urine biomarkers of OS, suggesting an association between intrarenal oxygenation and OS.

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“…For systemic inhibition of NHE-3, the newly developed inhibitor #4167, which is highly specific for NHE-3, was used [23,24]. NHE-I solution was prepared by dissolving it in sterile water just before the experiment.…”

Section: Nhe-3 Inhibitor Administration and Minipump Implantationmentioning

confidence: 99%

Protective role of NHE-3 inhibition in rat renal transplantation undergoing acute rejection

Reuter

Velić

Edemir

et al. 2008

Pflugers Arch - Eur J Physiol

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Acute rejection in renal transplantation disturbs solute and volume maintenance in humans accompanied by delayed graft function and poor prognosis. We recently reported that decreased expression and function of Na+/H+ exchanger type 3 (NHE-3) in proximal tubules and epithelial Na+ channels and aquaporin 2 in collecting ducts are major mechanisms involved in Na+ and water imbalances shortly after transplantation in rat undergoing acute rejection. We performed kidney transplantations in rats with bilaterally nephrectomized recipients with acute rejection and, in addition, systemically administered a specific inhibitor of NHE-3 (NHE-I). NHE inhibition in acute renal failure was shown to improve tubular function and recovery. The aim of this therapy was to reduce energy consumption of the graft and preserve NHE-3 function. Imbalances in electrolyte excretion declined in NHE-I-treated animals and NHE-3 activity was preserved. Observed NHE-I-dependent changes in electrolyte excretion, polyuria, and reduced protein reabsorption in the acute postoperative phase are predictors of favorable graft outcome in humans.

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Impact of renal transplantation on small vessel reactivity1

Cited by 31 publications

References 29 publications

Cyclosporine A Impairs Norepinephrine-Induced Vascular Contractility

Cyclosporine A Impairs Norepinephrine-Induced Vascular Contractility

BOLD-MRI assessment of intrarenal oxygenation and oxidative stress in patients with chronic kidney allograft dysfunction

Protective role of NHE-3 inhibition in rat renal transplantation undergoing acute rejection

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