RESUMEN
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.
Asunto(s)
Factor Natriurético Atrial/metabolismo , Estrógenos/metabolismo , FN-kappa B/metabolismo , Clorhidrato de Raloxifeno/farmacología , Tamoxifeno/farmacología , Transporte Activo de Núcleo Celular/efectos de los fármacos , Animales , Factor Natriurético Atrial/genética , Peso Corporal , Femenino , Corazón , Hemodinámica/efectos de los fármacos , Miocardio/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ovariectomía , Ratas , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Útero/efectos de los fármacosRESUMEN
The aim of this study was to compare, under resting conditions, the influence of chronic training in swimming or running on mean arterial pressure (MAP) and the involvement of the natriuretic peptide system in this response. Two-month-old male spontaneously hypertensive rats (SHR) were divided into three groups-sedentary (SD), swimming (SW) and running (RN)-and were trained for eight weeks under regimens of similar intensities. Atria tissue and plasma atrial natriuretic peptide (ANP) concentrations were measured by radioimmunoassay. ANP mRNA levels in the right and left atria as well as the natriuretic peptide receptors (NPR), NPR-A and NPR-C, mRNA levels in the kidney were determined by real-time PCR. Autoradiography was used to quantify NPR-A and NPR-C in mesenteric adipose tissue. Both training modalities, swimming and running, reduced the mean arterial pressure (MAP) of SHR. Swimming, but not running, training increased plasma levels of ANP compared to the sedentary group (P<0.05). Expression of ANP mRNA in the left atrium was reduced in the RN compared to the SD group (P<0.05). Expression of NPR-A and NPR-C in the kidneys of the SW group decreased significantly (P<0.05) compared to the SD group. Although swimming increased (125)I-ANP binding to mesenteric adipose tissue, displacement by c-ANF was reduced, indicating a reduction of NPR-C. These results suggest that the MAP reduction induced by exercise in SHR differs in its mechanisms between the training modalities, as evidenced by the finding that increased levels of ANP were only observed after the swimming regimen.