Neuronal Nitric Oxide Synthase-Dependent Amelioration of Diastolic Dysfunction in Rats with Chronic Renocardiac Syndrome

Lennart G. Bongartz, Siddarth Soni, Maarten-Jan Cramer, Paul Steendijk, Carlo A. J. M. Gaillard, Marianne C. Verhaar, Pieter A. Doevendans, Toon A. van Veen, Jaap A. Joles, Branko Braam*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

We have recently described the chronic renocardiac syndrome (CRCS) in rats with renal failure, cardiac dysfunction and low nitric oxide (NO) availability by combining subtotal nephrectomy and transient low-dose NO synthase (NOS) inhibition. Cardiac gene expression of the neuronal isoform of NOS (nNOS) was induced. Hence, we studied the role of nNOS, in vivo cardiac function and beta-adrenergic response in our CRCS model by micromanometer/conductance catheter. Left ventricular (LV) hemodynamics were studied during administration of dobutamine (dobu), the highly specific irreversible inhibitor of nNOS L-VNIO [L-N5-(1-Imino-3-butenyl)-ornithine], or both at steady state and during preload reduction. Rats with CRCS showed LV systolic dysfunction at baseline, together with prolonged diastolic relaxation and rightward shift of the end-systolic pressure-volume relationships. After L-VNIO infusion, diastolic relaxation of CRCS rats further prolonged. The time constant of active relaxation (tau) increased by 25 +/- 6% from baseline (p <0.05), and the maximal rate of pressure decrease was 36 +/- 7% slower (p <0.001). These variables did not change in controls. In our CRCS model, nNOS did not seem to affect systolic dysfunction. In summary, in this model of CRCS, blockade of nNOS further worsens diastolic dysfunction and L-VNIO does not influence inherent contractility and the response to dobu stress. (C) 2015 S. Karger AG, Basel.

Original languageEnglish
Pages (from-to)69-78
Number of pages10
JournalCardioRenal Medicine
Volume5
Issue number1
DOIs
Publication statusPublished - Feb-2015

Keywords

  • Diastolic function
  • Cardiorenal syndrome
  • Neuronal nitric oxide synthase
  • CHRONIC KIDNEY-DISEASE
  • LEFT-VENTRICULAR MYOCYTES
  • MYOCARDIAL-INFARCTION
  • HEART-FAILURE
  • SYSTOLIC DYSFUNCTION
  • CHRONIC UREMIA
  • CONTRACTILITY
  • MORTALITY
  • BETA(3)-ADRENOCEPTOR
  • DESENSITIZATION

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