RESUMEN
Fine-scale parameterizations based on shear and stratification are widely used to study the intensity and spatial distribution of turbulent diapycnal mixing in the ocean. Two well-known fine-scale parameterizations, Gregg-Henyey-Polzin (GHP) parameterization and MacKinnon-Gregg (MG) parameterization, are assessed with the full-depth microstructure data obtained in the North Pacific. The GHP parameterization commonly used in the open ocean succeeds in reproducing the dissipation rates over smooth topography but fails to predict the turbulence over rough topography. Failure of GHP parameterization over rough topography is attributed to the deviation of internal wave spectrum from the Garrett-Munk (GM) spectrum. The internal wave field over rough topography is characterized by energetic intermediate-scale and small-scale internal waves that are not described well by the GM model. The MG parameterization that is widely used in coastal environments is found to be successful in reproducing the dissipation rates over both smooth and rough topographies. The efficacy of GHP and MG parameterizations in evaluating the dissipation rates has been assessed. The result indicates that MG parameterization predicts the magnitude and variability of the dissipation rates better than the GHP parameterization.
RESUMEN
Adrenomedullin (ADM) has the vasodilatory properties and involves in the pathogenesis of vascular calcification. ADM could be degraded into more than six fragments in the body, including ADM(27-52), and we suppose the degrading fragments from ADM do the same bioactivities as derived peptides from pro-adrenomedullin. The present study carries forward by assessing the effects on vascular calcification of the systemic administration of ADM(27-52). The rat vascular calcific model was replicated with vitamin D3 and nicotine. ADM or/and ADM(27-52) were systemically administrated with mini-osmotic pump beginning at seventh day after the model replication for 25 days. Vascular calcific nodules histomorphometry, vascular calcium content, vascular calcium uptake, alkaline phosphatase activity, and osteopontin-mRNA quantification in aorta were assessed. ADM limited 40.2% vascular calcific nodules (P<0.01), did not effect on calcium content (P>0.05), reduced 44.4% calcium uptake (P<0.01), lowered 21.1% alkaline phosphatase activity (P<0.01), and regulated 40.9% downwards osteopontin-mRNA expression (P<0.01) in the aorta of rats with vascular calcification. ADM(27-52) receded 32.0% vascular calcific nodules (P<0.01), taken from 55.5% calcium content (P<0.01), did not affect calcium uptake (P>0.05), inhibited 22.5% alkaline phosphatase activity (P<0.01), and restrained 21.9% osteopontin-mRNA expression (P<0.01) in the aorta of rats with vascular calcification. Both of ADM and ADM(27-52) did interact on vascular calcification each other. ADM could partially antagonize the effects of ADM(27-52) in taking from calcium content (17.5%, P<0.01) and in receding vascular calcific nodules (18.6%, P<0.01). ADM could obviously enhance the action of ADM(27-52) in inhibiting alkaline phosphatase activity (14.4%, P<0.01) and in reducing calcium uptake (11.4%, P<0.01). ADM(27-52) could partially antagonize the effects of ADM on regulating downwards osteopontin-mRNA expression (17.0%, P<0.01). It is concluded that ADM(27-52) derived from ADM acts as an inhibitory agent on vascular calcification, with special mechanisms different from ADM derived from ADM progenitor molecule.
Asunto(s)
Aorta Torácica/metabolismo , Calcinosis/tratamiento farmacológico , Fragmentos de Péptidos/administración & dosificación , Adrenomedulina , Animales , Aorta Torácica/patología , Calcinosis/inducido químicamente , Calcinosis/metabolismo , Colecalciferol/toxicidad , Masculino , Nicotina/toxicidad , Agonistas Nicotínicos/toxicidad , Fragmentos de Péptidos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Aldosterone is involved in cardiovascular diseases such as hypertension and heart failure by inducing sodium retention and vascular remodeling, which is characterized by fibroblast proliferation and migration in adventitia. It is well known that aldosterone stimulates vascular smooth muscle cells and fibroblasts to produce and secrete adrenomedullin (ADM), a multiple functional peptide with an important cytoprotective effect against cardiovascular damage. We examined the effect of aldosterone on ADM production and secretion and its mRNA expression in rat aortic adventitia to study the paracrine/autocrine interaction between endogenous ADM and aldosterone. METHODS: ADM produced and secreted from adventitia stimulated by aldosterone in the absence or presence of spironolactone, RU486 or spironolactone together with RU486 were detected by radioimmunoassay, proliferation in adventitia cells was evaluated by the level of [H]-thymine incorporation, and preproADM gene expression was measured by semi-quantitative reverse transcriptase polymerase chain reaction. RESULTS: Adventitial ADM secretion and mRNA expression stimulated by aldosterone were concentration-dependent as was the inhibitive effect of ADM on aldosterone-induced proliferation. The induction of aldosterone in ADM secretion was mediated by mineralocorticoid receptor. Antagonists of specific receptors of calcitonin gene-related peptide (CGRP) receptor type 1 and ADM both potentiated the proliferation effect induced by aldosterone; and thiorphan, an inhibitor of the enzyme for ADM degradation, inhibited the adventitial [H]-thymine incorporation induced by aldosterone. ADM inhibited the activity of extracellular signal related kinase (ERK) stimulated by aldosterone. CONCLUSION: Aldosterone stimulates adventitia to produce and secrete ADM, which in turn, antagonizes the aldosterone-induced proliferation in adventitia.
Asunto(s)
Aldosterona/farmacología , Aorta/citología , Aorta/metabolismo , Tejido Conectivo/metabolismo , Péptidos/metabolismo , Adrenomedulina , Animales , Proliferación Celular/efectos de los fármacos , Tejido Conectivo/efectos de los fármacos , Interacciones Farmacológicas , Activación Enzimática/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Expresión Génica/efectos de los fármacos , Masculino , Técnicas de Cultivo de Órganos , Péptidos/efectos de los fármacos , Péptidos/genética , Precursores de Proteínas/genética , ARN Mensajero/metabolismo , Radioinmunoensayo , Ratas , Ratas Sprague-Dawley , Timina/metabolismoRESUMEN
Lysophosphatidic acid (LPA) is a bioactive phospholipid having growth factor-like activity on fibroblasts and is involved in cardiovascular diseases such as hypertension and heart failure by inducing vascular remodeling, characterized by fibroblast proliferation and migration in adventitia. Among various bioactive factors that LPA works with, adrenomedullin (ADM) is a multiple functional peptide with an important cytoprotective effect against cardiovascular damage. We studied rat aortic adventitia to explore the possible paracrine/autocrine interaction between endogenous ADM and LPA. LPA stimulation of the adventitia to secrete ADM and express its mRNA was concentration dependent. ADM inhibited LPA-induced proliferation in adventitial cells and attenuated the activity of mitogen-activated protein kinase (MAPK) stimulated by LPA. In contrast, treatment with specific antagonists of the ADM receptor potentiated the LPA-induced proliferation in adventitial cells. We concluded that LPA stimulates the adventitia to produce and secrete ADM, which in turn regulates the vascular biological effects of LPA.
Asunto(s)
Tejido Conectivo/efectos de los fármacos , Tejido Conectivo/metabolismo , Lisofosfolípidos/farmacología , Péptidos/metabolismo , Péptidos/farmacología , Adrenomedulina , Animales , Proliferación Celular/efectos de los fármacos , Tejido Conectivo/crecimiento & desarrollo , AMP Cíclico/metabolismo , ADN/biosíntesis , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Lisofosfolípidos/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Comunicación Paracrina/efectos de los fármacos , Péptidos/genética , Péptidos/fisiología , RatasRESUMEN
Adrenomedullin (ADM), a multifunction peptide with important roles in regulating cardiovascular homeostasis, has the vasodilatory properties and is of particular interest in the pathophysiology of sepsis. ADM levels in plasma and tissues are regulated by the proteolysis of neutral endopeptidase (NEP), the major enzyme of ADM degradation. We observed the NEP activity in the plasma, the activity and distribution of NEP and its mRNA expression in the tissues of rats in septic shock to study the possible role of NEP in elevating tissue ADM concentration during sepsis. ADM level increases progressively during sepsis except in the jejunum. Rats in early phase of shock (ES) showed diverse changes in tissue NEP activity. Plasma NEP activity, tissue NEP activity and its protein and mRNA expression in the left ventricle, aorta, jejunum and lung in the late phase of shock (LS) rats were lower than those in ES and the control, but no statistical change of NEP activity in the kidney was observed. The level of ADM was inversely correlated with NEP activity in the plasma, ventricle and aorta and positively correlated with NEP activity in the jejunum. Thus, in sepsis, the local concentration and action of ADM in tissues may be differentially regulated by NEP.
Asunto(s)
Neprilisina/metabolismo , Péptidos/metabolismo , Choque Séptico/metabolismo , Adrenomedulina , Animales , Aorta/química , Aorta/metabolismo , Glucemia/metabolismo , Presión Sanguínea , Enfermedades del Ciego/metabolismo , Enfermedades del Ciego/fisiopatología , Ciego/cirugía , Cromatografía Líquida de Alta Presión , Expresión Génica , Ventrículos Cardíacos/química , Ventrículos Cardíacos/metabolismo , Inmunohistoquímica , Yeyuno/química , Yeyuno/metabolismo , Riñón/química , Riñón/metabolismo , Ácido Láctico/sangre , Ácido Láctico/metabolismo , Ligadura , Modelos Lineales , Pulmón/química , Pulmón/metabolismo , Masculino , Neprilisina/sangre , Neprilisina/genética , Péptidos/análisis , Péptidos/sangre , Punciones , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Choque Séptico/fisiopatologíaRESUMEN
Adrenomedullin (ADM) is a multifunctional peptide with important roles in the cardiovascular system, especially in the adjustment of cardiovascular and renal homeostasis. ADM is present in plasma, organs and tissues, and its activity increases during hypertension. It remains unknown whether the clearance of this peptide is altered during hypertension. Neutral endopeptidase (NEP) is the major enzyme in ADM's degradation. We observed the activity and distribution of NEP and the expression of its mRNA in the plasma, cardiac ventricle, aorta, jejunum and kidney of spontaneously hypertensive rats (SHRs) in order to study the possible role of NEP in elevating tissue ADM concentrations during hypertension. ADM and NEP were diffuse in all tissues studied. The level of tissue ADM was generally higher in SHR tissues than in control tissues, except in the renal medulla, and its mRNA expression was higher in all tissues. Plasma NEP activity, general NEP activity and the expression of NEP mRNA in the left ventricle, aorta and jejunum in SHRs was lower than that of controls, and the level of ADM was inversely correlated with NEP activity. NEP activity and mRNA and protein expression in SHR kidneys were higher than in control kidneys; moreover, the ADM content was positively correlated with NEP activity in the renal cortex. NEP activity in the lung of SHRs did not differ from that of controls. Thus, in SHRs, the local concentration and action of ADM in the tissues may be differentially regulated by NEP.