title: Catecholamines increase lung edema clearance in rats with increased left atrial pressure.
abstract: During hydrostatic pulmonary edema, active Na(+) transport and alveolar fluid reabsorption are decreased. Dopamine (DA) and isoproterenol (ISO) have been shown to increase active Na(+) transport in rat lungs by upregulating Na(+)-K(+)-ATPase in the alveolar epithelium. We studied the effects of DA and ISO in isolated rat lungs with increased left atrial pressure (Pla = 15 cmH(2)O) compared with control rats with normal Pla (Pla = 0). Alveolar fluid reabsorption decreased from control value of 0.51 +/- 0.02 to 0.27 +/- 0.02 ml/h when Pla was increased to 15 cmH(2)O (P < 0.001). DA and ISO increased the alveolar fluid reabsorption back to control levels. Treatment with the D(1) antagonist SCH-23390 inhibited the stimulatory effects of DA (0.30 +/- 0.02 ml/h), whereas fenoldopam, a specific D(1)-receptor agonist, increased alveolar fluid reabsorption in rats exposed to Pla of 15 cmH(2)O (0.47 +/- 0.04 ml/h). Propranolol, a beta-adrenergic-receptor antagonist, blocked the stimulatory effects of ISO; however, it did not affect alveolar fluid reabsorption in control or DA-treated rats. Amiloride (a Na(+) channel blocker) and ouabain (a Na(+)-K(+)-ATPase inhibitor), either alone or together, inhibited the stimulatory effects of DA. Colchicine, which disrupts the cellular microtubular transport of ion-transporting proteins to the plasma membrane, inhibited the stimulatory effects of DA, whereas the isomer beta-lumicolchicine did not block the stimulatory effects of DA. These data suggest that DA and ISO increase alveolar fluid reabsorption in a model of increased Pla by regulating active Na(+) transport in rat alveolar epithelium. The effects of DA and ISO are mediated by the activation of dopaminergic D(1) receptors and the beta-adrenergic receptors, respectively.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago 60611, Illinois, USA.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Azzam
authors.forename: F J
authors.initials: FJ
authors.lastname: Saldias
authors.forename: A
authors.initials: A
authors.lastname: Comellas
authors.forename: K M
authors.initials: KM
authors.lastname: Ridge
authors.forename: D H
authors.initials: DH
authors.lastname: Rutschman
authors.forename: J I
authors.initials: JI
authors.lastname: Sznajder
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects / Q000502:physiology*; D001826:Body Fluids / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology*; D018818:Fenoldopam / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D011654:Pulmonary Edema / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*
chemical_list: D010042:Ouabain; D000584:Amiloride; D011433:Propranolol; D018818:Fenoldopam; D007545:Isoproterenol; D004298:Dopamine