PMID- 24759610
OWN - NLM
STAT- Publisher
LR  - 20191120
IS  - 1753-9455 (Electronic)
IS  - 1753-9447 (Linking)
VI  - 8
IP  - 4
DP  - 2014 Aug
TI  - Atorvastatin improves systolic function, but does not prevent the development of 
      dilated cardiomyopathy in streptozotocin-induced diabetic rats.
PG  - 133-144
AB  - BACKGROUND: Therapy with HMG-CoA reductase inhibitors (statins) has been 
      associated with a significant reduction in the number of major cardiovascular 
      (CV) events in diabetic patients. The mechanisms by which these drugs improve 
      cardiac status remain unclear. We assessed the effects of atorvastatin (10 
      mg/kg/day) on CV function in streptozotocin (STZ)-induced diabetic rats. METHODS: 
      Age-matched, nondiabetic rats were used as controls. Echocardiographic 
      parameters, systolic blood pressure (SBP), endothelial-dependent relaxation, 
      cardiac and vascular oxidative stress, perivascular fibrosis, and cholesterol 
      levels were evaluated after a 4-week atorvastatin treatment period. RESULTS: In 
      diabetic rats, SBP was higher than in controls. Atorvastatin decreased SBP in 
      diabetic rats by 14% (n = 10, p < 0.05), and significantly increased stroke 
      volume, ejection fraction, and cardiac output index. Whereas atorvastatin reduced 
      left ventricular end systolic volume (LVESV) by 50% (p < 0.05), it failed to 
      reduce left ventricular end diastolic volume (LVEDV). Total cholesterol was 
      higher in diabetic rats than in controls and atorvastatin was ineffective in 
      reducing cholesterol levels. The statin, however, decreased perivascular fibrosis 
      and media thickness, and the markers of oxidative stress malondialdehyde (MDA) 
      and 4-hidroxyalkenals (4-HAE) in aortic homogenates from diabetic rats. In 
      addition, atorvastatin improved endothelial function by increasing the E (MAX) 
      value of the acetylcholine-induced relaxation from 53.7 +/- 4.1% in untreated 
      diabetic to 82.1 +/- 7.0% in treated diabetic rats (n = 10, p < 0.05). L-NAME fully 
      abolished this improvement, suggesting that the increased vascular relaxation 
      with atorvastatin is NO-dependent. CONCLUSIONS: Whereas atorvastatin does not 
      reverse ventricular dilatation, it does have a positive hemodynamic effect on the 
      CV system of diabetic rats. This hemodynamic benefit is independent of 
      cholesterol levels, and is observed concomitantly with reduced oxidative stress, 
      vascular remodeling, and improved endothelial function. Together, these results 
      suggest that atorvastatin decreases the workload on the heart and improves 
      systolic performance in type 1 diabetic rats by reducing oxidative stress, 
      vascular tone, and systemic vascular resistance.
CI  - (c) The Author(s), 2014.
FAU - Quidgley, Jose
AU  - Quidgley J
AD  - Department of Physiology, School of Medicine, University of Puerto Rico, San 
      Juan, Puerto Rico.
FAU - Cruz, Nildris
AU  - Cruz N
AD  - Department of Physiology, School of Medicine, University of Puerto Rico, San 
      Juan, Puerto Rico.
FAU - Crespo, Maria J
AU  - Crespo MJ
AD  - Departments of Physiology and Anesthesiology, School of Medicine, University of 
      Puerto Rico, PO Box 365067, San Juan, PR 00936-5067, Puerto Rico 
      maria.crespo3@upr.edu.
LA  - eng
PT  - Journal Article
DEP - 20140423
PL  - England
TA  - Ther Adv Cardiovasc Dis
JT  - Therapeutic advances in cardiovascular disease
JID - 101316343
OTO - NOTNLM
OT  - atorvastatin
OT  - cardiac function
OT  - cholesterol
OT  - endothelial function
OT  - oxidative stress
OT  - type 1 diabetic rats
EDAT- 2014/04/25 06:00
MHDA- 2014/04/25 06:00
CRDT- 2014/04/25 06:00
PHST- 2014/04/25 06:00 [entrez]
PHST- 2014/04/25 06:00 [pubmed]
PHST- 2014/04/25 06:00 [medline]
AID - 1753944714531065 [pii]
AID - 10.1177/1753944714531065 [doi]
PST - ppublish
SO  - Ther Adv Cardiovasc Dis. 2014 Aug;8(4):133-144. doi: 10.1177/1753944714531065. 
      Epub 2014 Apr 23.