Statins Improve Cardiovascular Status in STZ‐Diabetic Rats

Abstract

Statin therapy has been associated with improved cardiac status in normocholesterolemic diabetic patients. The underlying mechanisms remain unknown. We compared the effects of daily administration of 10mg/kg atorvastatin (AV), simvastatin (SV), or pravastatin (PV) on CV function of streptozotocin (STZ)-diabetic rats. Systolic blood pressure (SBP), and echocardiographic parameters were evaluated after 4 weeks of treatment. The effect of acute incubation with statins on the Ach-induced relaxation was also evaluated in NE-precontracted aortic rings. SBP was significantly higher in diabetic than in age-matched non-diabetic rats (CT). SV decreased SBP in diabetic rats by 21% (N=10, P<0.05), whereas AV and PV did not modify this parameter. Statins increased cardiac output (CO) by 112 % (AV), 137% (SV), and 75% (PV) (N=10, P<0.05). Stroke volume and ejection fraction were also significantly increased by all the statins. Furthermore, the EMAX value for the Ach-induced relaxation was reduced in diabetic rats (53.7±4%) when compared to CT (74.6±3%) (N=10, P<0.05), and acute incubation of aortic rings with AV (5μM, 45 min) increased EMAX to 71.5±5% (N=4, P<0.05). These results indicate that statins have positive hemodynamic effects in diabetic rats which may be secondary to improvement on endothelial function and reduction on vascular tone and systemic peripheral resistance. Supported by RCMI Grant G12RR03051