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1.
Int Heart J ; 55(1): 78-83, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24463928

RESUMEN

We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion. Wall movement velocity of the left ventricular base was assessed by tissue Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later. Pathological lesions were identified by deposits of carbon particles. Animals were divided into two groups according to the infused dose of adrenaline. The small-dose group (group S, n = 15) received 1-10 µg and the large-dose group (group L, n = 23) received 15-60 µg of adrenaline. Adrenaline infusion induced premature ventricular contractions followed by monomorphic ventricular tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group S. Wall movement velocity of the left ventricular base decreased just after adrenaline infusion, remained low after 1 week, and recovered to near-baseline levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits of carbon particles were frequently observed on the left ventricular basal portion, almost always associated with the mitral valve and papillary muscles, but were never observed in the apical area. Lesions involving all areas of the left ventricular basal portion were observed in 22 of 23 animals in group L, but in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits with ventricular tachycardias induced by a single injection of adrenaline.


Asunto(s)
Cardiomiopatías/etiología , Taquicardia Ventricular/complicaciones , Animales , Cardiomiopatías/patología , Modelos Animales de Enfermedad , Epinefrina/administración & dosificación , Femenino , Miocardio/patología , Conejos , Simpatomiméticos/administración & dosificación , Taquicardia Ventricular/inducido químicamente , Taquicardia Ventricular/patología
2.
Nihon Ronen Igakkai Zasshi ; 50(3): 409-12, 2013.
Artículo en Japonés | MEDLINE | ID: mdl-23979350

RESUMEN

Although macrocytic anemia can develop in patients with acute blood loss, such anemia in very old patients is uncommon. In this report, we describe the course of an 89-year-old woman who had a rapid recovery from macrocytic anemia by medication only after acute blood loss due to a gastric ulcer. She had been treated with antihypertensive drugs for the previous 28 years at our outpatient clinic, and was admitted because of acute anemia 6 days after she had experienced tarry stool. Her hemoglobin (Hb) count and mean corpuscular volume (MCV) were 8.4 g/dl, and 103 fl, respectively. A gastroscopic examination indicated that the tarry stool originated from a fresh gastric ulcer. She was treated with an iron preparation, a diuretic and a proton pump inhibitor. The anemia was rapidly improved to Hb 10.5 g/dl and MCV 106 fl in one week, and to Hb 14.5 g/dl and MCV 99 fl in 4 weeks. At admission, she had slight pleural effusion and slight edema associated with an increase in her plasma brain natriuretic peptide (BNP) level (323 pg/ml), and her left ventricular ejection fraction was 76% based on the echocardiography findings, which are signs of the high-output heart failure without remarkable left ventricular diastolic dysfunction (E/e': 11.2). However, these signs improved rapidly, and her BNP level thereafter decreased to 114 pg/ml within four weeks.


Asunto(s)
Anemia Macrocítica/etiología , Gasto Cardíaco Elevado/etiología , Insuficiencia Cardíaca/etiología , Úlcera Péptica Hemorrágica/complicaciones , Enfermedad Aguda , Anciano de 80 o más Años , Femenino , Humanos , Úlcera Gástrica/complicaciones
3.
Eur J Pharmacol ; 587(1-3): 237-42, 2008 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-18457832

RESUMEN

Although antihypertensive drugs confer improvement in endothelial dysfunction and protection from atherogenesis in hypertension, different classes of antihypertensive drugs may elicit different degrees of vasculoprotective effects. We have investigated the effects of a long-acting calcium antagonist, benidipine, and an angiotensin AT(1) receptor antagonist, losartan, on the vascular damage observed in OLETF rats, an animal model of metabolic syndrome. At 34 weeks of age, OLETF rats were treated with either benidipine (3 mg/kg/day, per os) or losartan (25 mg/kg/day, per os) for 8 weeks. The extent of blood pressure reduction, restoration endothelium-dependent aortic relaxation, and elevation of serum nitrite/nitrate concentration did not differ significantly between benidipine- and losartan-treated OLETF rats. Benidipine and losartan also reduced the aortic expression of transforming growth factor-beta1 mRNA and thickening of the vascular wall to a similar extent. Increased cardiac fibrosis was also inhibited by both benidipine and losartan. These data suggest that, when used in an antihypertensive dose, benidipine is as effective as losartan in restoring vascular endothelial function and in suppressing of cardiovascular remodeling in an animal model of metabolic syndrome.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Dihidropiridinas/uso terapéutico , Endotelio Vascular/patología , Losartán/uso terapéutico , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/patología , Animales , Aorta Torácica/efectos de los fármacos , Fibrosis , Corazón/efectos de los fármacos , Técnicas In Vitro , Relajación Muscular/efectos de los fármacos , Miocardio/patología , Nitratos/sangre , Nitritos/sangre , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ratas , Ratas Endogámicas OLETF , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
4.
Hypertens Res ; 30(2): 195-202, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17460390

RESUMEN

Due to recent discoveries of novel genes involved in iron metabolism, our understanding of the molecular mechanisms underlying iron metabolism has dramatically increased. We have previously shown that the administration of angiotensin II alters iron homeostasis in the rat kidney, which may in turn aggravate angiotensin II-induced renal damage. Here we have investigated the effect of angiotensin II administration on the localization and expression of transferrin receptor (TfR), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN), and hepcidin mRNA in the rat kidney. Weak expression of TfR, DMT1, FPN, and hepcidin mRNA was observed in the kidneys of control rats. In contrast, after 7 days of angiotensin II infusion by osmotic minipump, the expression of these mRNAs was more widely distributed. Staining of serial sections revealed that some, but not all, of the renal tubular cells positive for these genes contained iron deposits in the kidney of angiotensin II-infused animals. Real-time polymerase chain reaction (PCR) showed that the mRNA expression of TfR, iron-responsive element-negative DMT1, FPN, and hepcidin mRNA increased ~1.9-fold, ~1.7-fold, ~2.3-fold, and ~4.7-fold, respectively, after angiotensin II infusion as compared with that of untreated controls, and that these increases could be suppressed by the concomitant administration of losartan. Our data demonstrate that these genes were unequivocally expressed in the kidney and could be regulated by angiotensin II infusion. The relative contribution, if any, of these genes to renal and/or whole-body iron homeostasis in various disorders in which the renin angiotensin system is activated should be investigated in future studies.


Asunto(s)
Angiotensina II/administración & dosificación , Péptidos Catiónicos Antimicrobianos/genética , Proteínas de Transporte de Catión/genética , Hierro/metabolismo , Riñón/efectos de los fármacos , Receptores de Transferrina/genética , Animales , Regulación de la Expresión Génica , Hepcidinas , Riñón/química , Riñón/metabolismo , Metabolismo de los Lípidos/genética , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas
5.
Arterioscler Thromb Vasc Biol ; 25(11): 2282-8, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16100038

RESUMEN

OBJECTIVE: We have investigated whether long-term administration of angiotensin (Ang) II causes ferritin induction and iron accumulation in the rat aorta, and their possible relation to regulatory effects on gene expression and vascular function in Ang II-infused animals. METHODS AND RESULTS: Sprague-Dawley rats were given Ang II for 7 days via subcutaneously implanted osmotic minipumps. Ang II infusion caused a >20-fold increase in ferritin protein expression over control values. Immunohistochemistry showed that Ang II infusion markedly increased the ferritin expression in the aortic endothelial and adventitial cells, with some of the latter being identified as monocytes/macrophages. Prussian blue staining showed that stainable iron was observed in the adventitial layer of aorta from Ang II-infused animals, but not in the endothelial layer. Chelation of iron suppressed aortic induction of ferritin and also the oxidative stress markers, heme oxygenase-1 and 4-hydroxynonenal-modified protein adducts. In addition, iron chelation attenuated Ang II-induced impairment of aortic relaxations in response to acetylcholine and sodium nitroprusside and suppressed upregulation of mRNA levels of monocyte chemoattractant protein-1. Iron chelation also partially attenuated the medial thickening and perivascular fibrosis induced by Ang II infusion for 4 weeks. CONCLUSIONS: Ang II infusion caused ferritin induction and iron deposition in the aortas. These phenomena might have a role in the regulation of gene expression, impairment of vascular function, and arterial remodeling induced by Ang II, which are presumably mediated in part by enhancement of oxidative stress.


Asunto(s)
Enfermedades de la Aorta/tratamiento farmacológico , Deferoxamina/farmacología , Ferritinas/metabolismo , Hipertensión/complicaciones , Quelantes del Hierro/farmacología , Sobrecarga de Hierro/tratamiento farmacológico , Aldehídos/metabolismo , Angiotensina II/farmacología , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Aorta/patología , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/patología , Apoferritinas , Quimiocina CCL2/metabolismo , Ferritinas/genética , Hemo-Oxigenasa 1/metabolismo , Hipertensión/inducido químicamente , Hierro/metabolismo , Sobrecarga de Hierro/inducido químicamente , Sobrecarga de Hierro/patología , Complejo Hierro-Dextran/farmacología , Masculino , Norepinefrina/farmacología , Estrés Oxidativo/efectos de los fármacos , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Receptores de Transferrina/genética , Regulación hacia Arriba/efectos de los fármacos , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos
6.
Hypertens Res ; 33(3): 263-8, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20057486

RESUMEN

Unfavorable lipid accumulation may occur in the kidneys in the presence of metabolic syndrome and diabetes. The aim of this study was to investigate whether excess lipids would accumulate in the kidneys of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of metabolic syndrome. From 34 weeks of age, OLETF rats were treated orally with a calcium channel blocker, benidipine (3 mg kg(-1) per day), or an AT1 receptor blocker, losartan (25 mg kg(-1) per day), for 8 weeks. Blood pressure was slightly but significantly higher in the untreated OLETF rats (149+/-4 mm Hg) than in Long-Evans Tokushima Otsuka (LETO) rats (136+/-2 mm Hg), and both losartan (135+/-3 mm Hg) and benidipine (138+/-3 mm Hg) reduced blood pressure in OLETF rats to a level comparable to that in LETO rats. Tissue content of triglycerides (TG) was greater in OLETF rats than in LETO rats (6.24+/-3.77 and 2.85+/-1.32 microg mg(-1) x tissue, respectively), and both losartan and benidipine reduced these values. Histological analysis showed lipid droplets in tubular cells in which increased dihydroethidium fluorescence was present. Expression of peroxisome proliferator-activated receptor-alpha, PGC-1alpha and uncoupling protein-2 was found to be higher in OLETF rats than in LETO rats; however, the expression of these genes was not altered by treatment with either antihypertensive drug. In contrast, both losartan and benidipine increased the amount of total and phosphorylated forms of AMP kinase and the expression of carnitine palmitoyltransferase-1 (CPT-1). In conclusion, treatment of OLETF rats with losartan and benidipine reduced the tissue content of TG, decreased the production of superoxide and regulated the expression of genes related to fatty acid oxidation such as AMP-activated protein kinase and CPT-1 in the kidneys.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Dihidropiridinas/farmacología , Riñón/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Losartán/farmacología , Síndrome Metabólico/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Carnitina O-Palmitoiltransferasa/metabolismo , Colesterol/metabolismo , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Endogámicas OLETF , Ratas Long-Evans , Superóxidos/metabolismo , Triglicéridos/metabolismo
7.
Eur J Pharmacol ; 604(1-3): 87-92, 2009 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-19109942

RESUMEN

Accumulation of lipids in the heart may cause cardiac dysfunction in various disorders, such as obesity and diabetes. In the current study, we have investigated whether administration of angiotensin II or norepinephrine induces accumulation of lipids and/or changes in the expression of genes related to lipid metabolism in the rat heart. Lipid deposition was found in myocardial, vascular wall, and perivascular cells of the angiotensin II-infused rat heart, and superoxide generation was increased in these lipid-positive cells. By contrast, intracardiac lipid deposition was not found in the heart of norepinephrine-induced hypertensive rats. Triglyceride content in the heart tissue of angiotensin II-infused rats increased more than 3-fold as compared with untreated controls. Losartan completely, but hydralazine only partially, suppressed the angiotensin II-induced intracardiac lipid deposition and increase in tissue triglyceride content. Administration of angiotensin II upregulated the mRNA expression of sterol regulatory element-binding protein-1c and fatty acid synthase, but downregulated that of uncoupling protein 2 and 3, in a manner dependent on the angiotensin AT(1) receptor. Collectively, these results suggest that angiotensin II may be involved in modulating both intracardiac lipid content and lipid metabolism-related gene expression, in part via an angiotensin AT(1) receptor-dependent and pressor-independent mechanism.


Asunto(s)
Angiotensina II/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Miocardio/metabolismo , Norepinefrina/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Western Blotting , Expresión Génica/efectos de los fármacos , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Metabolismo de los Lípidos/genética , Lípidos/sangre , Masculino , Miocardio/patología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Superóxidos/metabolismo
9.
Lab Invest ; 86(12): 1285-92, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17043664

RESUMEN

Lipid accumulation in the kidney is a marker of tissue damage and may play a role in the development of renal injury. We have previously shown that long-term administration of angiotensin II in rats causes increased expression of transforming growth factor-beta1, coupled with an accumulation of lipids in the tubular and vascular wall cells in the kidney. In this study, we examine the regulation of expression of platelet-derived growth factor (PDGF) and its receptor system and their co-localization with lipid deposits in the kidneys of angiotensin II-infused rats. Real-time RT-PCR showed that expression of PDGF-B, PDGF-D, and PDGF receptor-beta (PDGFR-beta) mRNA was increased by angiotensin II infusion, and in situ hybridization showed the co-localization of these mRNAs. Tubular cells that had increased PDGF-B mRNA expression were positive for lipid deposition and also for cellular proliferation, which was indicated by the presence of proliferating cell nuclear antigen. By contrast, in the kidneys of angiotensin II-infused rats, apoptosis occurred in tubular cells that contained deposits of iron but not lipids. The deposition of lipids and upregulation of PDGF-B, PDGF-D, and PDGFR-beta induced by administration of angiotensin II were all suppressed by the selective angiotensin II type 1 (AT(1)) receptor antagonist losartan, but not by the nonspecific vasodilator hydralazine. The findings that lipid accumulation, upregulation of PDGF-B, PDGF-D, and PDGFR-beta, and cellular proliferation were topologically associated and regulated in an AT(1) receptor-dependent manner in the kidney of angiotensin II-infused rats suggests that these phenomena are related.


Asunto(s)
Angiotensina II/fisiología , Riñón/metabolismo , Linfocinas/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Proteínas Proto-Oncogénicas c-sis/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Angiotensina II/farmacología , Animales , Antihipertensivos/farmacología , Apoptosis/fisiología , Proliferación Celular , Regulación de la Expresión Génica/efectos de los fármacos , Hidralazina/farmacología , Hibridación in Situ , Hierro/metabolismo , Riñón/fisiología , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/fisiología , Losartán/farmacología , Masculino , Norepinefrina/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Vasoconstrictores/farmacología
10.
Hypertension ; 46(5): 1180-5, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16203876

RESUMEN

Abnormal lipid metabolism may play a role in progressive renal failure. We studied whether lipid accumulation occurs and whether lipid deposits are colocalized with transforming growth factor-beta1 (TGF-beta1) in the kidney of angiotensin II-infused animals. Oil red O staining showed marked lipid deposition in the tubular epithelial and vascular wall cells of angiotensin II-treated but not in norepinephrine-treated rats. Histological analyses showed that increased amounts of superoxide and intense TGF-beta1 mRNA expression were present in lipid-positive tubular epithelial cells in angiotensin II-infused animals. Protein expression of sterol regulatory element-binding protein 1 (SREBP-1) and mRNA expression of fatty acid synthase in the kidney were &3 times and 1.5 times, respectively, higher in angiotensin II-treated rats than in controls. Treatment of angiotensin II-infused animals with an iron chelator, deferoxamine, attenuated the angiotensin II-induced increases in renal expression of SREBP-1 and fatty acid synthase and normalized the lipid content in the renal cortical tissues. Abnormal lipid metabolism may be associated with upregulation of TGF-beta1 expression and aberrant iron homeostasis in the kidneys of angiotensin II-infused animals.


Asunto(s)
Angiotensina II/farmacología , Riñón/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Animales , Deferoxamina/farmacología , Ácido Graso Sintasas/genética , Regulación de la Expresión Génica , Hibridación in Situ , Hierro/metabolismo , Quelantes del Hierro/farmacología , Metabolismo de los Lípidos/genética , Lípidos/sangre , Masculino , Inhibidor 1 de Activador Plasminogénico/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Coloración y Etiquetado , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/antagonistas & inhibidores , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Superóxidos/metabolismo , Distribución Tisular , Factor de Crecimiento Transformador beta1
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