Blockade of neuronal nitric oxide synthase (nNOS) worsened diastolic dysfunction in rats with chronic renocardiac syndrome, increasing active relaxation time constant (tau) by 25 ± 6%.
Does nNOS inhibition with L-VNIO worsen diastolic dysfunction in rats with chronic renocardiac syndrome?
In a rat model of chronic renocardiac syndrome, blockade of neuronal nitric oxide synthase worsens diastolic dysfunction without affecting systolic function or beta-adrenergic response.
Absolute Event Rate: 0% vs 0%
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 L-VNIO does not influence inherent contractility and the response to dobu stress.
Bongartz et al. (Thu,) reported a other. Blockade of neuronal nitric oxide synthase (nNOS) worsened diastolic dysfunction in rats with chronic renocardiac syndrome, increasing active relaxation time constant (tau) by 25 ± 6%.