Paroxetine Alters Cardiac Stress Markers in Rats with Aortic Regurgitation

Abstract

Background: Aortic regurgitation (AR) is a valvulopathy that causes volume overload to the heart leading to left ventricle dilation and eccentric hypertrophy. A common co-morbidity associated with cardiovascular disease is depression. We have previously shown that paroxetine, a selective serotonin re-uptake inhibitor widely prescribed as antidepressant, improves cardiac contractility by preserving fractional shortening (FS) of AR rat hearts.In failing hearts, decrease of the ability of the myocardium to generate an effective shortness velocity is well correlated with the shift of myosin isoform distribution from α to β-MyHC expression. In order to understand the molecular mechanism involved in the improvement of FS after paroxetine treatment, we verified the expression of genes involved in heart contractility and hypertrophy.Methods and Findings: Male Wistar rats were submitted to AR surgery, by retrograde puncture of the aortic valves leaflets, or sham surgery. Morphofunctional variables of the hearts were analyzed by echocardiograms at weeks 4 and 8 after the induction of AR.At week 8 the animals were euthanized for tissue collection and posterior analysis of gene expression by RTq-PCR. Paroxetine treatment for 4 weeks in AR rats reduced the gene expression of β-MyHC and its myomiRs (miR-208 and miR-499). BNP, a molecular biomarker of hypertrophy, also showed their gene expression reduction after paroxetine treatment. Conclusion:These results suggest that paroxetine treatment improves FS in AR hearts through reductions in the expression of several genes involved with cardiac contractility and hypertrophy.

Disrupted fluid balance and baroreflex sensitivity in acute aortic regurgitation

“…Male Wistar rats (260 to 280 g) had sham or AR surgeries induced by multiple retrograde puncture of the aortic valve leaflets under anesthesia (ketamine 80 mg/kg of bw plus xylazine 7mg/Kg bw, Vetbrands, Jacareí-SP) as described elsewhere 24,25,26 . All procedures were in accordance with the Animal Care and Use policies of the Institute of Biosciences of Botucatu, according to the Brazilian College of Animal Experimentation (COBEA, number 141/09) policies.…”

“…Animals that failed to meet these criteria were excluded. We analysed LV dimensions, wall thickness, ejection fraction, diastolic function, and cardiac output (i.e., ejection volume in the LV outflow tract-heart rate), as previously reported 24,25,26 .…”