Abstract P3103: Heart Failure In Menopause: Treatment With Rock Inhibitor And Atorvastatin

Abstract

In advanced age, women tend to develop heart failure with preserved ejection fraction (HFpEF) due to estrogen depletion. The signaling pathway of ROCK is involved in cardiac complications consequent to female aging. Thus, this work investigated the comparative effects of atorvastatin and ROCK inhibitor, fasudil on the treatment of HFpEF induced by oophorectomy (OVX) in spontaneously hypertensive rats (SHR). Protocols were approved by the Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Under anesthesia with ketamine (80 mg/kg, i.p.) and xylazine (15 mg/kg, i.p.), female SHR were submitted to OVX procedure and after 8 wks were randomly orally treated with either vehicle or atorvastatin (40 mg/kg) or fasudil (10 mg/kg) during 4 wks. At the end of treatment, hemodynamic parameters were evaluated using echocardiography and LV catheterization. Cardiac tissues were collected for histologic analysis. Cardiac hypertrophy was reversed by treatment with atorvastatin or fasudil. Increased systolic pressure of LV was observed in SHR-OVX group (149.2 ± 7.9 mmHg), which was partially reduced by fasudil (123.4 ± 7.4 mmHg) and normalized by atorvastatin (94.5 ± 3.9 mmHg). Reduction of the increased diastolic dysfunction observed by echocardiogram was confirmed, since the recovery of the increased LV end diastolic pressure of SHR-OVX (32.1 ± 1.8 mmHg) occurred after treatment with atorvastatin (22.4 ± 9.6 mmHg) and fasudil (11.9 ± 2.4 mmHg). Fibrosis was observed because of the increased collagen deposition in SHR-OVX (6.2 ± 0.1%), with partial reduction with fasudil (4.4 ± 0.3%) and normalization after treatment with atorvastatin (1.9 ± 0.7%). Cell proliferation was evaluated using the p38 marker, where the percentage of nuclei marked was determined in relation to the total, through immunohistochemical technique. An increase in nuclear p38 in the SHR-OVX group was observed (23.2 ± 3.2%), however, the treatment with atorvastatin (12.1 ± 1.7%) and fasudil (5.3 ± 1.3%) reduced the nuclear p38 detection. In conclusion, atorvastatin and fasudil promoted recovery of HFpEF induced by estrogen depletion in SHR. Inhibition of ROCK signalling by atorvastatin could be involved in the reduction of diastolic dysfunction observed in OVX-SHR group.