Possible role of poly(ADP-ribose) polymerase in pathological and physiological cardiac hypertrophy.
The present study was designed to investigate the effect of 5-aminoisoquinoline, a specific poly(ADP-ribose) polymerase (PARP) inhibitor, in partial abdominal aortic constriction (PAAC) for 4 weeks it induced pathological and chronic swimming training (CST) for 8 weeks it induced physiological cardiac hypertrophy. 5-Aminoisoquinoline (0.3 mg/kg/day and 3 mg/kg/day, i.p.) treatment was started 3 days before PAAC and CST, and it was continued for 4 weeks after PAAC and 8 weeks after initiation of CST. The left ventricular (LV) function and LV hypertrophy were assessed by measuring LVDP, dp/dtmax, dp/dtmin, ratio of LV weight to body weight (LVW/BW), LV wall thickness (LVWT), LV collagen content, LV protein content, and LV RNA concentration. Further, venous pressure (VP) and mean arterial blood pressure (MABP) were recorded. The PAAC, but not CST, produced LV dysfunction by decreasing LVDP, dp/dtmax, dp/dtmin, and increasing LV collagen content. Further, PAAC and CST were noted to produce LV hypertrophy by increasing LVW/BW, LVWT, LV protein content, and LV RNA concentration. Moreover, in contrast to CST, PAAC significantly increased VP and MABP. The 5-aminoisoquinoline, a potent selective inhibitor of PARP, significantly attenuated PAAC-induced LV dysfunction, LV hypertrophy, increase in VP and MABP. On the other hand, treatment with 5-aminoisoquinoline did not modulate CST-induced physiological cardiac hypertrophy. These results implicate PARP in PAAC-induced LV dysfunction and pathological cardiac hypertrophy. However, PARP may not be involved in CST-induced physiological cardiac hypertrophy.
Balakumar
P
P
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India. pbala2002@rediffmail.com
Singh
M
M
D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism; D003251:Constriction, Pathologic; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*
C411425:5-aminoisoquinolinone; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012313:RNA; D003094:Collagen