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.

Higher physiological doses of nandrolone decanoate do not influence the Bezold-Jarish reflex control of bradycardia.

BACKGROUND: We investigated the influence of short-term treatment with supraphysiological doses of an anabolic-androgenic steroid on the Bezold-Jarisch reflex (BJR) control of heart rate (HR) and whether this treatment induced cardiac hypertrophy and anabolic effects in rats. METHODS: Male rats were treated with nandrolone decanoate (10 mg/kg(-1) body weight/4 weeks; DECA) or vehicle control (CON). After 4 weeks of treatment, BJR was evaluated by bradycardia responses that were elicited by serotonin administration (2-32 microg/kg(-1)). Mean arterial pressure (MAP) was assessed and cardiac hypertrophy was determined by the left ventricle weight/body weight (LVW/BW) ratio. Histological analyses of LV and the measurement of the total body protein content of the animals were performed. RESULTS: Nandrolone decanoate (ND) treatment had no effect on the MAP (CON=105+/-5; DECA=110+/-3 mmHg). However, the mean basal HR of DECA animals was significantly lower than that of control animals (CON = 381+/-14; DECA=324+/-12 bpm; p<0.01). ND did not change the sensitivity of the BJR. The LVW/BW ratio indicated significant hypertrophy of the LV in DECA animals (CON=1.76+/-0.04; DECA=2.0+/-0.04 mg/g; p<0.01). Histological and morphometrical analyses demonstrate that there is also modest myocyte hypertrophy (CON=14.5+/-1.5; DECA=20.0 +/- 0.9 myocyte nuclei/field; p<0.05). However, the Masson-trichromic-stained samples showed an enhancement of collagen deposits on the LV matrix. CONCLUSIONS: We concluded that 4 weeks ND treatment induced an anabolic effect and the beginnings of LV remodeling, mainly due to excessive collagen deposition in the cardiac extracellular matrix. However, the treatment did not influence BJR control of bradycardia, an effect that could be explained by an enhanced efferent vagal tonus in DECA animals.