Angiotensin converting enzyme inhibition prevents polyploidization of cardiomyocytes in spontaneously hypertensive rats with left ventricular hypertrophy.
Polyploidization of cardiomyocyte nuclei is a physiological phenomenon that increases in pathological conditions such as myocardial hypertrophy. The purpose of this study was to evaluate the potential benefit of the angiotensin converting enzyme (ACE) inhibitor quinapril in reversing the polyploidization of cardiomyocyte nuclei in spontaneously hypertensive rats (SHR) with established left ventricular hypertrophy (LVH). Sixteen week-old male SHR were treated with oral quinapril (average dose 10 mg/kg per day) for 20 weeks. Sixteen- and 36-week-old untreated SHR and 16- and 36-week-old normotensive Wistar-Kyoto (WKY) rats were used as controls. Nuclear polyploidization was determined by DNA flow cytometry of frozen tissues from the left ventricle, at least 20,000 nuclei being measured in each sample. The rates of tetraploidy in the 16- and 36-week-old SHR groups were 2.8 per cent (range 2.16-3 per cent) and 5.4 per cent (range 4.9-5.9 per cent), respectively. Treated SHR had a similar rate of DNA tetraploidy to the 16- and 36-week-old WKY rat groups: 1.8 per cent (range 1.5-2.3 per cent), 1.55 per cent (range 1.5-1.6 per cent), and 1.5 per cent (range 1.4-1.6 per cent), respectively. The differences in the percentage of tetraploid cardiomyocytes between the SHR untreated groups and the SHR treated group were statistically significant (P < 0.05). Regression of LVH and normalization of blood pressure were observed in treated rats. These results indicate that DNA tetraploidy in the myocardium of SHR increases with hypertrophy and decreases on quinapril treatment. It is suggested that ACE inhibition modifies nuclear processes involved in myocyte growth in arterial hypertension.
Panizo-Santos
A
A
Department of Pathology, Clínica Universitaria, Facultad de Medicina, Pamplona, Spain.
Sola
J J
JJ
Pardo-Mindán
F J
FJ
Hernández
M
M
Cenarruzabeitia
E
E
Díez
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D007546:Isoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011003:Ploidies; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077583:Quinapril