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


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: R(2) = 0.518; P < 0.001) and heart rate (R(2) = 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.


CONCLUSIONS
Collectively, these results support a role for 4HNE in the pathophysiological events linked to disease progression in SHRs.
Asselin
C
C
Department of Biomedical Sciences, University of Montreal, Montreal, Quebec, Canada.
Shi
Y
Y
Clément
R
R
Tardif
J C
JC
Des Rosiers
C
C
D000447:Aldehydes / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003971:Diastole / Q000187:drug effects / Q000502:physiology*; D004562:Electrocardiography; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D000447:Aldehydes; D000975:Antioxidants; C027576:4-hydroxy-2-nonenal; D011341:Probucol