RESUMEN
OBJECTIVES: To investigate the effect of selective ß3-adrenoreceptor agonist BRL-37344 on L-type Ca(2+) current (Ica,L) and mRNA expression of L-type Ca(2+) channel α2δ-2 (Cacna2d2) in rats with chronic heart failure (CHF). METHODS: Twenty-four male Wistar rats were divided into normal control (n=6) and CHF group (n=18), which were further divided into CHF control and BRL group (0.4nmol/kg, IV, twice weekly for four weeks). Echocardiography was performed to assess the structure and function of the left atrium (LA). RESULTS: The LA in the BRL group (4.4 ± 0.2mm) was larger than in the normal control (3.5 ± 0.3mm, P<0.01) or CHF control (4.0 ± 0.2mm, P<0.05) group. The LA ejection fraction in the BRL group (36.2 ± 4.2%) was lower than in the normal control (58.0 ± 3.1%, P<0.01) or CHF control group (42.3 ± 4.8%, P<0.05). There was no difference in Ica,L density between the BRL group and CHF control group (8.3 ± 1.7 vs. 8.2 ± 2.6 pA/pF, P>0.05), which was higher than in the normal control group (6.0 ± 1.8 pA/pF, P<0.01). There was no difference in the mRNA expression of α2δ-2 (Cacna2d2) between the BRL group and CHF control group (0.264 ± 0.005 vs. 0.243 ± 0.017, P>0.05), which was also higher than in the normal control group (0.137 ± 0.013, P<0.01). CONCLUSION: ß3-Adrenoreceptor stimulation with BRL-37344 was associated with an increase in LA diameter and a decrease in LA function in chronic heart failure. These structural and function changes were not related to Ica,L or L-type Ca(2+) channel α2δ-2 (Cacna2d2) subunit in the LA myocytes.
Asunto(s)
Canales de Calcio Tipo L/metabolismo , Canales de Calcio/metabolismo , Calcio/metabolismo , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Receptores Adrenérgicos beta 3/metabolismo , Agonistas Adrenérgicos beta/farmacología , Animales , Enfermedad Crónica , Etanolaminas/farmacología , Atrios Cardíacos/metabolismo , Atrios Cardíacos/fisiopatología , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Masculino , Ratas , Ratas WistarRESUMEN
OBJECTIVES: To investigate the expression of ß(3)-adrenergic receptor (ß(3)-AR) in the atrium of rats with chronic heart failure (CHF). METHODS: The heart failure rat model was established by aortic constriction. Thirty-six male Wistar rats were divided into Sham group (n = 10) and heart failure model group (n = 26), which were further divided into CHF control (CHF group) and BRL group. The rats in the BRL group were treated with a selective ß(3)-AR agonist, BRL-37344 (4.0 nmol/kg, twice weekly) for 4 weeks. RESULTS: In the BRL group, the left ventricular end-systolic pressure (83.21 ± 13.0 vs 101.50 ± 12.12 mm Hg) and the absolute values of the maximal rate of rise and fall of left ventricular pressure ([±dP/dtmax] 2.81 ± 0.04 vs 0.35 ± 0.04 and -2.72 ± 0.06 vs -3.33 ± 0.06) were lower than in the CHF group (P < .01). The left atrial mass index (LAMI) in the BRL group (0.4132 ± 0.0306) was higher than that in the CHF (0.3212 ± 0.0136) or Sham group (0.2683 ± 0.0145; P < .01). The levels of the left atrial ß(3)-AR messenger RNA (mRNA) expression in the BRL group (0.932 ± 0.055) was higher than that in the CHF (0.706 ± 0.043) or Sham group (0.310 ± 0.020; P < .01). In all animals, there was a positive correlation between the level of ß(3)-AR mRNA expression and the left or right atrial mass index (correlation coefficient ranged from 0.744 to 0.937). CONCLUSION: There is a significant increase in the ß(3)-AR mRNA expression in the atrium of rats with heart failure. The level of ß(3)-AR mRNA expression was associated with the AMI and was enhanced by a selective ß(3)-AR agonist, BRL-37344.
Asunto(s)
Atrios Cardíacos/metabolismo , Insuficiencia Cardíaca/metabolismo , Receptores Adrenérgicos beta 3/biosíntesis , Regulación hacia Arriba , Animales , Enfermedad Crónica , Atrios Cardíacos/patología , Insuficiencia Cardíaca/patología , Masculino , ARN Mensajero/biosíntesis , Ratas , Ratas Wistar , Receptores Adrenérgicos beta 3/genética , Regulación hacia Arriba/genéticaRESUMEN
AIM: To investigate whether total Panax notoginseng saponins (PNS) could protect endothelium of rabbit iliac artery against balloon endothelial denudation (BED) injury. METHODS: The morphology changes of the endothelium were observed with scanning electron microscope (SEM) and hematoxylin and eosin stain after BED of rabbit iliac artery at 0, 4, 6, and 8 week respectively. Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) was also determined by immunohistochemistry. PNS 10, 30, and 50 mg/kg were administered iv per day from 2 d before to 4 weeks after operation. RESULTS: The endothelium was denudated completely after BED. At the 4th week the endothelium was repaired in some degree, then recovered gradually at 6 and 8 week. The degree of intimal thickening at 4 week was significantly greater than that at 0, 6, or 8 week. The sequence of VEGF or MMP-2 staining from strong to weak was 4, 6, 0, 8 week, and normal control. However at 4 week, endothelial regeneration in PNS 30 and 50 mg/kg groups was significantly faster than that in saline group. The intimal thickness was significantly decreased and expressions of VEGF and MMP-2 were both down-regulated in PNS 30 or 50 mg/kg groups compared with saline control group. CONCLUSION: PNS promoted the endothelial regeneration and reduced ECM thickening, which was related to regulation of the expression of VEGF and MMP-2. PNS may have sustained antirestenotic effect after BED.
