title: Neuronal nitric oxide synthase-dependent amelioration of diastolic dysfunction in rats with chronic renocardiac syndrome.
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 β-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.
authors.affiliation: Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands ; Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Lennart G
authors.initials: LG
authors.lastname: Bongartz
authors.affiliation: Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Siddarth
authors.initials: S
authors.lastname: Soni
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maarten-Jan
authors.initials: MJ
authors.lastname: Cramer
authors.affiliation: Department of Cardiology and Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.affiliation: Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Carlo A J M
authors.initials: CA
authors.lastname: Gaillard
authors.affiliation: Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Verhaar
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.affiliation: Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Toon A
authors.initials: TA
authors.lastname: van Veen
authors.affiliation: Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Joles
authors.affiliation: Division of Nephrology and Immunology, Department of Medicine, University of Alberta, Edmonton, Alta., Canada ; Department Physiology, University of Alberta, Edmonton, Alta., Canada.
authors.forename: Branko
authors.initials: B
authors.lastname: Braam
keywords: Cardiorenal syndrome; Diastolic function; Neuronal nitric oxide synthase