Adenovirus-mediated atrial natriuretic protein expression in the lung protects rats from hypoxia-induced pulmonary hypertension. 2001

V Louzier, and S Eddahibi, and B Raffestin, and I Déprez, and M Adam, and M Levame, and M Eloit, and S Adnot
INSERM U492 and Département de Physiologie, Hôpital Henri Mondor, AP-HP, 94010 Créteil, France.

Endogenous as well as exogenous atrial natriuretic peptide (ANP) attenuates the development of chronic hypoxic pulmonary hypertension (CHPH) in rats. We built a recombinant adenovirus type 5 containing ANP cDNA under the control of the Rous sarcoma virus long terminal repeat (Ad.ANP). The efficiency of this vector in delivering the ANP gene was first examined in rat primary cultures of pulmonary vessel smooth muscle cells (SMCs) in comparison with Ad.beta GAL. Conditioned medium collected from Ad.ANP-infected cells (1000 TCID(50)/cell) contained 5 x 10(9) M immunoreactive ANP and elicited relaxation of isolated rat pulmonary arteries preconstricted with phenylepinephrine. To examine the effects of adenovirus-mediated ANP expression in the CHPH rat lung, Ad.ANP or Ad.beta GAL was administered via the tracheal route. Immunoreactive ANP was detected in bronchoalveolar fluid as early as 4 days and until 10-17 days after Ad.ANP administration (5 x 10(8) TCID(50)). Lung ANP immunostaining was mainly localized in bronchial and alveolar epithelial cells. As compared with Ad.beta GAL-treated controls, rats given Ad.ANP (5 x 10(8) TCID(50)) on the day before a 2-week exposure to hypoxia (10% O(2)) had lower values for pulmonary artery pressure (32.1 +/- 1.93 vs. 35.5 +/- 2 mmHg, p < 0.01) and Fulton's index (0.52 +/- 0.089 vs. 0.67 +/- 0.12, p < 0.001) and less severe right ventricular hypertrophy and distal vessel muscularization. These results suggest that induction of ANP expression in the lung may hold promise in the treatment of pulmonary hypertension.

UI MeSH Term Description Entries
D006976 Hypertension, Pulmonary Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES. Pulmonary Hypertension
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009320 Atrial Natriuretic Factor A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS. ANF,ANP,Atrial Natriuretic Peptide,Atrial Natriuretic Peptides,Atriopeptins,Auriculin,Natriuretic Peptides, Atrial,ANF (1-126),ANF (1-28),ANF (99-126),ANF Precursors,ANP (1-126),ANP (1-28),ANP Prohormone (99-126),ANP-(99-126),Atrial Natriuretic Factor (1-126),Atrial Natriuretic Factor (1-28),Atrial Natriuretic Factor (99-126),Atrial Natriuretic Factor Precursors,Atrial Natriuretic Factor Prohormone,Atrial Natriuretic Peptide (1-126),Atrial Pronatriodilatin,Atriopeptigen,Atriopeptin (1-28),Atriopeptin (99-126),Atriopeptin 126,Atriopeptin Prohormone (1-126),Cardiodilatin (99-126),Cardiodilatin Precursor,Cardionatrin I,Cardionatrin IV,Prepro-ANP,Prepro-CDD-ANF,Prepro-Cardiodilatin-Atrial Natriuretic Factor,Pro-ANF,ProANF,Proatrial Natriuretic Factor,Pronatriodilatin,alpha ANP,alpha-ANP Dimer,alpha-Atrial Natriuretic Peptide,beta-ANP,beta-Atrial Natriuretic Peptide,gamma ANP (99-126),gamma-Atrial Natriuretic Peptide,Natriuretic Peptide, Atrial,Peptide, Atrial Natriuretic,Peptides, Atrial Natriuretic,Prepro ANP,Prepro CDD ANF,Prepro Cardiodilatin Atrial Natriuretic Factor,Pro ANF,alpha ANP Dimer,alpha Atrial Natriuretic Peptide,beta ANP,beta Atrial Natriuretic Peptide,gamma Atrial Natriuretic Peptide
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004837 Epinephrine The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS. Adrenaline,4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol,Adrenaline Acid Tartrate,Adrenaline Bitartrate,Adrenaline Hydrochloride,Epifrin,Epinephrine Acetate,Epinephrine Bitartrate,Epinephrine Hydrochloride,Epinephrine Hydrogen Tartrate,Epitrate,Lyophrin,Medihaler-Epi,Acetate, Epinephrine

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