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Abstract: PO2146

Pharmacological Sympathetic Denervation of the Kidney with Angiotensin II Receptor Blockade?

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Rodionova, Kristina, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
  • Ditting, Tilmann, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
  • Hilgers, Karl F., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
  • Ott, Christian, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
  • Schmieder, Roland E., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
  • Schiffer, Mario, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
  • Amann, Kerstin U., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
  • Veelken, Roland, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
Background


A putative interaction between angiotensin II (Ang II) and the renal sympathetic nervous system has been described. We tested the hypothesis that the angiotensin II receptor inhibitor candesartan mimicks a functional renal sympathetic denervation not distinguishable from surgical renal nerve ablation.

Methods


Measurement of arterial blood pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), glomerular filtration (GFR), renal plasma flow (RPF), urine volume and urinary sodium. To assess neural control of volume homeostasis, 21 days after the induction of congestive heart failure (CHF) via myocardial infarction rats underwent volume expansion (0.9% NaCL; 10% body weight) to decrease RSNA. CHF rat and controls with or without renal denervation (DNX) or pretreated with the angiotensin II type 1 receptor antagonist candesartan (0.5 ug i.v.) were studied.

Results


CHF rats excreted only 68+5% of the volume load in 90 min. CHF rats pretreated with candesartan or after DNX excreted from 92% to 103% like controls. Decrease of RSNA induced by volume expansion were impaired in CHF rats but unaffected by candesartan pointing to an intrarenal drug effect. GFR and RPF were not significantly different in controls or CHF rendering mere hemodynamic effects on sodium and water excretion unlikely. 0.5 mg candesartan did not inhibit the pressor response to i.v. Ang II as compared to higher blood pressure lowerig doses.

Conclusion

The prominent function of increased RSNA – retaining salt and water - could no longer be observed after renal ANG II receptor blockade in CHF rats mimicking renal nerve ablation.Since inhibitors of the renin-angiotensin system are nowadays standard treatment of patients with CHF and hypertension, the role of efferent sympathetic denervation in these patients needs further meticulous scrutiny.

Funding

  • Government Support - Non-U.S.