Higher circulating 4-hydroxynonenal–protein thioether adducts correlate with more severe diastolic dysfunction in spontaneously hypertensive rats

Abstract

Objective: Accumulating evidence supports a role of 4-hydroxynonenal (4HNE) in oxidative-stress related diseases, but its specific contribution to disease development remains to be clarified. Further to our finding of high circulating 4HNE–protein thioether adducts (4HNE-P) in spontaneously hypertensive rats (SHRs), we aimed at correlating 4HNE-P with cardiac function and testing the impact of antioxidant therapy.

Materials and Methods: The lipoperoxidation inhibitor probucol (10 mg/kg/day) or vehicle (corn oil) were administered daily (i.p.) for 4 weeks in 18-week-old SHRs (9 rats/group). Cardiac functions were assessed by echocardiography and 4HNE-P by gas chromatography/mass spectrometry.

Results: Diastolic dysfunction worsened in SHRs receiving vehicle as reflected by changes (P < 0.05) in indexes of left ventricular relaxation (increased isovolumic relaxation time) and compliance (increased E-wave deceleration rate; EDR). Higher circulating 4HNE-P correlated with diastolic dysfunction (EDR: R² = 0.518; P < 0.001) and heart rate (R² = 0.225; P < 0.05). Probucol prevented the deterioration of diastolic function, while lowering the mean and median of circulating 4HNE-P by 21% and 35%, respectively.

Conclusion: Collectively, these results support a role for 4HNE in the pathophysiological events linked to disease progression in SHRs.

Keywords:

• 4-HYDROXYNONENAL-PROTEIN THIOETHER ADDUCTS
• DIASTOLIC DYSFUNCTION
• SPONTANEOUSLY HYPERTENSIVE RATS
• PROBUCOL