Nandrolone alter left ventricular contractility and promotes remodelling involving calcium-handling proteins and renin-angiotensin system in male SHR.

AIMS: Hypertension is a highly prevalent disease that has been correlated to severe organ damage and mortality. However, the role of androgens in hypertension is controversial. The aim of this study was to evaluate the cardiac effects of the nandrolone decanoate (NDL) in male SHR. MAIN METHODS: At 12 weeks of age, male SHR rats were separated into three groups: Control (CON), Nandrolone 10 mg/kg twice weekly (NDL), and NDL plus Enalapril 10 mg/kg/day (NDL-E) groups. The animals were treated for 4 weeks. Haemodynamic parameters were acquired through ventricular catheter implantation. The left ventricle was stained with haematoxylin/eosin or picrosirius red. Western blot analysis of TNF-α, ACE, AT1R, ß1-AR, PLB, p-PLBser16 and SERCA2a was performed. KEY FINDINGS: Nandrolone increased hypertension in SHR rats and enalapril reduced blood pressure to values below those of the control. NDL increased +dP/dtmax, -dP/dtmax and cardiac hypertrophy, which were prevented in the NDL-E group. Cardiac collagen deposition was increased in the NDL group, with this effect being attenuated by enalapril in NDL-E animals. TNF-α, ACE, AT1R and ß1-AR proteins were increased in the NDL, and enalapril decreased them, except for TNF-α. The ratio p-PLBser16/PLB revealed an increase after nandrolone, which was prevented in the NDL-E group. The SERCA2a expression protein and SERCA2a/PLB were increased in NDL animals, which did not occur in the NDL-E group. SIGNIFICANCE: Nandrolone has distinct effects on cardiac function and remodelling in male SHR, altering the hypertension development process in the heart through modulation of calcium handling proteins and the renin-angiotensin system.

The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen improve ANP levels and decrease nuclear translocation of NF-kB in estrogen-deficient rats.

BACKGROUND: The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen are used for the treatment of osteoporosis and cancer, respectively, in women. The impairment of both the Atrial Natriuretic Peptide (ANP) cell signaling system and the translocation of nuclear factor-kappa B (NF-kB) to the cell nucleus are associated with detrimental cardiovascular effects and inflammation. The effects of SERMs on these parameters in the cardiac tissue of estrogen-deficient rats has not been reported. METHODS: We investigated the effects of raloxifene and tamoxifen on ANP signaling, p65 NF-kB nuclear translocation, cardiac histology and contractility. Female rats were divided into five groups: control (SHAM), ovariectomized (OVX), OVX-treated 17-ß-estradiol (E), OVX-treated raloxifene (RLX) and OVX-treated tamoxifen (TAM). The treatments started 21days after ovariectomy and continued for 14days. RESULTS: Ovariectomy reduced ANP mRNA in the left atrium (LA), decreased the content of ANP protein in the LA and in plasma, and increased the level of p65 NF-kB nuclear translocation in the left ventricle. Both 17-ß-estradiol and SERMs were able to reverse these alterations, which were induced by the estrogen deficient state. The hemodynamic and cardiac structural parameters analyzed in the present work were not modified by the interventions. CONCLUSIONS: Our study demonstrates, for the first time, the additional benefits of raloxifene and tamoxifen in an estrogen-deficient state. These include the normalization of plasmatic and cardiac ANP levels and cardiac p65 NF-kB translocation. Therefore, these treatments promote cardiovascular protection and may contribute to the prevention of cardiac dysfunction observed long-term in postmenopausal women.