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1.
Respiration ; 72(2): 189-96, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15824530

RESUMO

BACKGROUND: Although aerosolized beta-adrenergic agonists have been used as a therapy for the resolution of pulmonary edema, the mechanisms of catecholamine clearance from the alveolar spaces of the lung are not well known. OBJECTIVE: To determine whether catecholamine clearance from the alveolar spaces is correlated with the fluid transport capacity of the lung. METHODS: Albumin solution containing epinephrine (10(-7)M) or norepinephrine (10(-7)M) was instilled into the alveolar spaces of isolated rat and human lungs. Alveolar fluid clearance rate was estimated by the progressive increase in the albumin concentration over 1 h. Catecholamine clearance rate was estimated by the changes in catecholamine concentration and alveolar fluid volume over 1 h. RESULTS: The norepinephrine clearance rate was faster than the epinephrine clearance rate in the rat and human lungs. In the rat lungs, amiloride (a sodium channel blocker) caused a greater decrease in alveolar fluid clearance and epinephrine clearance rate than propranolol (a nonselective beta-adrenergic antagonist). Although propranolol and phentolamine (an alpha-adrenergic antagonist), and 5-(N-ethyl-N-isoprophyl)amiloride (a Na+/H+ antiport blocker) changed neither the alveolar fluid clearance nor the norepinephrine clearance rate, amiloride and benzamil (a sodium channel blocker) decreased both clearance rates. As in the rat lungs, amiloride decreased alveolar fluid and norepinephrine clearance rates in the human lungs. CONCLUSION: These results indicate that the catecholamine clearance rate from the alveolar spaces is correlated with alveolar fluid clearance in rat and human lungs.


Assuntos
Amilorida/análogos & derivados , Catecolaminas/farmacocinética , Alvéolos Pulmonares/metabolismo , Agonistas alfa-Adrenérgicos/administração & dosagem , Agonistas alfa-Adrenérgicos/farmacocinética , Antagonistas Adrenérgicos alfa/administração & dosagem , Antagonistas Adrenérgicos alfa/farmacocinética , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/farmacocinética , Amilorida/administração & dosagem , Amilorida/farmacocinética , Animais , Catecolaminas/administração & dosagem , Epinefrina/administração & dosagem , Epinefrina/farmacocinética , Líquido Extracelular/metabolismo , Humanos , Técnicas In Vitro , Instilação de Medicamentos , Masculino , Norepinefrina/administração & dosagem , Norepinefrina/farmacocinética , Fentolamina/administração & dosagem , Fentolamina/farmacocinética , Propranolol/administração & dosagem , Propranolol/farmacocinética , Alvéolos Pulmonares/citologia , Ratos , Ratos Sprague-Dawley , Bloqueadores dos Canais de Sódio/administração & dosagem , Bloqueadores dos Canais de Sódio/farmacocinética , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores
2.
J Pharmacol Sci ; 95(4): 420-5, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15286427

RESUMO

Uridine 5'-triphosphate (UTP) increases chloride secretion followed by fluid movement into the proximal airspaces. However, little is known about whether UTP affects fluid movement in the distal airspaces. We studied the effect of UTP on basal and stimulated alveolar fluid clearance in the isolated rat lungs. Isosmotic 5% albumin solution was instilled into the alveolar spaces of isolated rat lungs, which were then inflated with 100% oxygen at an airway pressure of 7 cmH(2)O. Alveolar fluid clearance was measured by the progressive increase in albumin concentrations over 1 h. Although UTP (10(-9) - 10(-6) M) did not increase alveolar fluid clearance, UTP (10(-5) - 10(-3) M) and isoproterenol (10(-5) M), a beta-adrenergic agonist, increased alveolar fluid clearance by 40% and 120% of the basal values, respectively. A combined treatment of UTP (10(-4) M, 10(-3) M) and isoproterenol increased alveolar fluid clearance by 280% of the basal value. The effects of UTP in the presence and absence of isoproterenol were abolished by blockers of a P2 purinoceptor and chloride channels. These results indicate that UTP stimulates alveolar fluid clearance in the distal airspaces of rat lungs.


Assuntos
Água Extravascular Pulmonar/metabolismo , Alvéolos Pulmonares/metabolismo , Uridina Trifosfato/fisiologia , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Interações Medicamentosas , Água Extravascular Pulmonar/efeitos dos fármacos , Glibureto/farmacologia , Técnicas In Vitro , Isoproterenol/farmacologia , Masculino , Nitrobenzoatos/farmacologia , Propranolol/farmacologia , Alvéolos Pulmonares/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Suramina/farmacologia
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