RESUMEN
AIM: To observe the regression effect of tetrandrine (Tet) and enalapril (Ena) on vascular morphological changes in renovascular hypertensive (RH) rats. METHODS: Renovascular hypertension was induced by two kidney one clip (2K1C) operation. The morphometric measurements were performed in the aorta, caudal artery, renal arterioles, coronary arterioles and mesenteric arterioles. RESULTS: The wet weight of aorta, caudal artery and femoral artery of RH rats (18 weeks after 2K1C operation) were greater than those of sham-operated rats. The media thickness, lumen diameter, cross section of media, media over lumen ratio and the wet weight of abdomen aorta, caudal artery, coronary arterioles, renal arterioles and mesenteric arterioles were significantly increased, which were more significant in arterioles with the diameter smaller than 70 microns. There were no significant change in the number of the smooth muscle cells (VSMC) in most vessel wall, except in renal arterioles, where the number of smooth muscle cells were significantly increased. After Tet (50 mg.kg-1.d-1, p.o.) or Ena (6 mg.kg-1.d-1, p.o.) treated for 9 weeks from week 9 after 2K1C operation, almost all the changes in the media thickness, the media to lumen ratio, the cross section of media and the wet weight were ameliorated. CONCLUSION: In RH rats, mainly a hypertrophic and rearrangement remodeling in the wall of arteries and arterioles was observed with a proliferation of VSMC in renal arterioles. Tet and Ena were shown to regress vascular remodeling by markedly attenuating these changes in renovascular hypertensive rats.
Asunto(s)
Alcaloides/uso terapéutico , Antihipertensivos/uso terapéutico , Bencilisoquinolinas/uso terapéutico , Enalapril/uso terapéutico , Hipertensión Renovascular/tratamiento farmacológico , Animales , Aorta Abdominal/patología , Arteriolas/efectos de los fármacos , Arteriolas/patología , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Hipertensión Renovascular/patología , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Masculino , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Tetrandrine (Tet) is an alkaloid isolated from the Chinese herb Radix of Stephaniae tetrandrae S Moore. Cardiac and vascular remodeling confers a very definite risk of increased cardiovascular morbidity and mortality. Remodeling reversal has been achieved in human and experimental animals treated with some antihypertensive drugs but not all. This review will focus on cardiovascular remodeling and therapeutic effects of Tet. Three models, SHR, RHR (high renin), and DOCA-Salt HR (low renin) were used. Left ventricular and vascular remodeling had been developed in rats with 8-week untreated hypertension. Tet was administrated by ig 50 mg/kg/d for 9 weeks. Tet lowered SBP, left ventricular weight to body weight ratio, vascular media thickness, media to lumen ratio, cardiac and vascular wet weight, and collagen content. Tet decreased markedly the density and total number of dihydropyridine binding sites and also decreased Ca2+ overload in myocardium and vessels. Tet improved haemodynamic changes during remodeling special diastolic function such as LV compliance and stiffness, increased cardiac myosin ATPase activity and Na+-K+, Ca2+ ATPase activity, and normalized vascular reactivity. Tet inhibited proliferation of vascular smooth muscle cells, induced and sensitized VSMCs to pro-apoptosis stimulation, improved the endothelial function, and increased NO production. These results suggest that Tet was not only an anti-hypertensive drug but also an excellent drug to reverse cardiac and vascular remodeling.
Asunto(s)
Alcaloides/farmacología , Bencilisoquinolinas/farmacología , Sistema Cardiovascular/efectos de los fármacos , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Remodelación Ventricular/efectos de los fármacos , Alcaloides/aislamiento & purificación , Animales , Antihipertensivos/farmacología , Apoptosis/efectos de los fármacos , Bencilisoquinolinas/aislamiento & purificación , Calcio/metabolismo , Humanos , Músculo Liso Vascular/citología , Músculo Liso Vascular/enzimologíaRESUMEN
AIM: To study the effects of praeruptorin C (pra-C) on proliferation of cattle aortic smooth muscle cells (SMC). METHODS: The DNA synthesis of SMC was measured using the incorporation of [3H]thymidine([3H]TdR). Cell cycle phase was evaluated by flow cytometry and cytotoxicity was evaluated by measuring lactic dehydrogenase (LDH) activity. RESULTS: Whether or not treated with angiotensin II (Ang-II), SMC proliferation was suppressed by pra-C in a concentration-dependent manner at range from 0.001 micromol/L to 10 micromol/L. The inhibitory effects appeared to be related to G1-S block in cell cycle traverse while the LDH activities did not change dramatically. CONCLUSION: Pra-C can completely inhibit SMC proliferation induced by Ang II and partly inhibit the growth of SMC- induced by bovine serum, which is important in prevention and treatment of vascular hyperplastic disease.
Asunto(s)
Cumarinas/farmacología , Medicamentos Herbarios Chinos/farmacología , Músculo Liso Vascular/efectos de los fármacos , Angiotensina II/farmacología , Animales , Animales Recién Nacidos , Aorta Torácica/citología , Bovinos , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Separación Celular , Células Cultivadas , ADN/biosíntesis , L-Lactato Deshidrogenasa/metabolismo , Músculo Liso Vascular/citologíaRESUMEN
AIM: To investigate the preventive and reversional effect of praeruptorum caumarin compound on left ventricular hypertrophy in renovascular hypertensive rats (RHR) and its mechanism. METHODS: The two-kidney-one-clip (2K1C) RHR model was used. The blood pressure, wet weight of the left ventricle, surface area of myocardial cells, resting [Ca2+]i level and Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase activity of myocardial membrane and mitochondria were measured. RESULTS: Praeruptorum caumarin 30 mg.kg-1.d-1 was given ig for 9 weeks from the 6th or 9th week after operation in the preventive or regressive group. The blood pressure, left ventricle wet weight and area of myocardial cells of the preventive and regressive group were significantly reduced than that of the LVH group. The resting [Ca2+]i of the both praeruptorum caumarin treated groups (121 +/- 13, 133 +/- 9 nmol.L-1) were lower than that of the LVH group (158 +/- 7 nmol.L-1). The KCl-induced [Ca2+]i elevation was decreased more significantly in preventive and regressive group than that of the hypertrophic myocytes. The activity of Na+, K(+)-ATPase and Ca2+, Mg(2+)-ATPase increased by 40% and 93% in the preventive group, 28.4% and 48.8% in regressive group than that of the LVH group. CONCLUSION: Praeruptorum caumarin was shown to prevent and reverse hypertrophy of LVH by lowering [Ca2+]i and increasing the ATPase activity.
Asunto(s)
ATPasa de Ca(2+) y Mg(2+)/metabolismo , Calcio/metabolismo , Cumarinas/farmacología , Hipertensión Renovascular/metabolismo , Miocitos Cardíacos/efectos de los fármacos , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Apiaceae/química , Separación Celular , Cumarinas/aislamiento & purificación , Cumarinas/uso terapéutico , Modelos Animales de Enfermedad , Hipertensión Renovascular/complicaciones , Hipertensión Renovascular/patología , Hipertensión Renovascular/prevención & control , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/patología , Mitocondrias/enzimología , Miocitos Cardíacos/metabolismo , Plantas Medicinales/química , Ratas , Ratas Sprague-DawleyRESUMEN
AIM: To investigate the effects of praeruptorin C (Pra-C) on smooth muscle cell (SMC) hypertrophy, intracellular calcium ([Ca2+]i), nitric oxide (NO) content and influence on cellular signal transduction in isolated cultured rat smooth muscle cell (SMC). METHODS: Hypertrophied smooth muscle cells (HSMCs) were induced by angiotensin II (Ang II), cell area was measured under inverted microscope. Nitric oxide (NO) concentration was measured using Griess method. [Ca2+]i was measured using Fura-2/AM. The responses to [Ca2+]i elevation stimulated by KCl (60 mmol.L-1 or norepinephrine (10 mumol.L-1) were observed by incubation with phorbol 12-myristate 13-acetate (PMA), staurosporine (ST), the agonist and inhibitor of protein kinase C (PKC), and pertussis toxin (PTX), the sensitive toxin of Gi. RESULTS: The cell area of SMCs were decreased by 39.01% (P < 0.001) and NO content of SMCs were significantly increased in Pra-C + Ang II group. In presence of 60 mmol.L-1 KCl or 10 mumol.L-1 NE, [Ca2+]i of SMCs in Pra-C + Ang II group was significantly decreased than that of Ang II group (P < 0.001) and closed to the normal group. Incubation of SMCs with PMA, ST and PTX, [Ca2+]i of SMCs in Ang II group was increased by PMA and decreased by ST and PTX, but that of Pra-C + Ang II group was similar to the normal group. CONCLUSION: These findings suggest that Pra-C can reduce vascular hypertrophy in isolated rat HSMCs, and this is associated with improvement of SMCs [Ca2+]i level, NO content and cellular signal transdution of PKC and Gi.
Asunto(s)
Calcio/metabolismo , Cumarinas/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Óxido Nítrico/metabolismo , Transducción de Señal/efectos de los fármacos , Angiotensina II , Animales , Aorta/patología , Bloqueadores de los Canales de Calcio/farmacología , Células Cultivadas , Femenino , Hipertrofia/inducido químicamente , Hipertrofia/patología , Masculino , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/patología , Ratas , Ratas Sprague-DawleyRESUMEN
AIM: To investigate the effects of ginkgolide B (GB) on proliferation of bovine aortic smooth muscle cells (SMC) and its related mechanisms. METHODS: After pretreating with GB or the mixture of ginkgolide A and B (GA:GB) at 37 degrees C for 0.5 h, the VSMC were treated with or without angiotensin II (Ang II) for 24 h. The proliferation of SMC was evaluated by 3H-thymidine incorporation and the cell cycle phase was measured by flow cytometry. Cytotoxicity was reflected by MTT and lactate dehydrogenase (LDH) activity of the supernatant. RESULTS: Whether or not treated with Ang II, GB and GA:GB were shown to suppress SMC proliferation in concentration-dependent fashion at concentrations ranging from 10(-9) mol.L-1 to 10(-5) mol.L-1. The inhibitory effects appeared to be related to a G1-->S block in cell cycle traverse. CONCLUSION: The suppression of SMC proliferation by GB might not only be contributed by blockage of the PAF receptor activity.