Biomedical subjects

Yochai Adir

Publications and source records attributed to Yochai Adir.

22 records · Page 2Linked to original sources

PubMed2003

Regulation of lung edema clearance by dopamine.

In the kidney, dopamine inhibits Na,K-ATPase, which results in natriuresis because less Na+ is reabsorbed by the proximal and distal tubules. In contrast, dopamine stimulates Na,K-ATPase activity in the alveolar epithelium, leading to increased alveolar fluid reabsorption. Importantly, dopamine increases alveolar fluid reabsorption not only in normal alveolar epithelium but also in models of lung injury. Dopamine short-term regulation of alveolar epithelial Na,K-ATPase occurs via D1 receptor activation, protein kinase C and protein phosphatase 2A pathways, leading to increased Na,K-ATPase activity by recruiting sodium pumps from the intracellular compartment to the basolateral membranes. Conversely, D2 receptor activation by long-term dopamine regulates (approximately 24 hours) alveolar epithelial Na,K-ATPase via the MAPK pathway, [figure: see text] which results in de novo synthesis of Na,K-ATPase proteins. Conceivably, by increasing Na,K-ATPase activity and promoting alveolar fluid reabsorption, dopamine can be of clinical relevance for the treatment of patients with acute hypoxemic respiratory failure due to pulmonary edema.

Animals↗

PubMed2003

Pulmonary edema following closed-circuit oxygen diving and strenuous swimming.

Acute pulmonary edema may be induced by diving and strenuous swimming. We report the case of a diver using closed-circuit, scuba equipment who developed acute dyspnea, hemoptysis, and hypoxemia following a dive in 18 degreesC (64.4 degrees F) water and physical exertion during the swim back to shore. With the growing popularity of recreational scuba diving, emergency physicians are liable to be faced with increasing numbers of diving-related medical problems. Diving-induced pulmonary edema should be included in the differential diagnosis of acute hypoxemia, sometimes accompanied by acid-base abnormalities, when this is seen in a diver.

Adult↗

PubMed2002

Na,K-ATPase overexpression improves alveolar fluid clearance in a rat model of elevated left atrial pressure.

BACKGROUND: Acute elevation of left atrial pressure (LAP) increases extravascular water and impairs active Na(+) transport in rat lungs. We have reported that overexpression of Na,K-ATPase subunit genes in the alveolar epithelium increases alveolar fluid clearance (AFC) in normal and injured rat lungs with normal LAP. We reasoned that adenovirus-mediated transfer of an Na,K-ATPase beta-subunit gene to the alveolar epithelium could improve AFC in rat lungs in the presence of acutely elevated LAP. METHODS AND RESULTS: Normal rats were infected with 4x10(9) plaque-forming units of E1a(-)/E3(-) recombinant adenoviruses that contained a cytomegalovirus promoter coupled to a rat Na,K-ATPase beta(1)-subunit cDNA (adbeta(1)) or no cDNA (adNull) 7 days before study. Na,K-ATPase alpha(1)- and beta(1)-subunit abundance in basolateral cell membranes isolated from the peripheral lung was significantly increased in adbeta(1)-infected lungs compared with sham and adNull-infected controls. In all groups, elevation of LAP reduced membrane-bound Na,K-ATPase abundance; however, abundance in adbeta(1)-infected lungs remained greater than in controls. AFC, measured with a fluid-filled isolated lung preparation in the presence of elevated LAP (15 cmH(2)O), in Na,K-ATPase beta(1)-subunit-overexpressing lungs was up to 100% greater than in controls and was not different from rats studied at normal LAP (0 cmH(2)O). CONCLUSIONS: These data suggest that alveolar overexpression of an Na,K-ATPase beta(1)-subunit can counteract downregulation of membrane-bound solute transporters owing to elevated pulmonary vascular pressures and can restore active Na(+) transport and AFC in this rat model of acute hydrostatic pulmonary edema.

Adenoviridae↗

PubMed2002

Effects of beta2-adrenergic receptor overexpression on alveolar epithelial active transport.

beta-Adrenergic receptor (betaAR) agonists accelerate the clearance of edema from the alveolar airspace by increasing the function of epithelial transport proteins, including epithelial Na(+) channels and Na,K-adenosinetriphosphatases. To improve our understanding of the role of the beta(2)AR in regulating alveolar fluid clearance, we used an adenoviral-mediated gene transfer strategy to effect significant increases in membrane-bound beta(2)AR number and function in the alveolar epithelium of normal rats. Alveolar fluid clearance in beta(2)AR-overexpressing lungs, measured by means of an isolated lung model in the absence of catecholamine supplementation, was 100% greater than in controls. These findings were associated with significant increases of epithelial Na(+) channel function and Na,K-adenosine triphosphatase function in the peripheral lung. Experiments performed with adrenalectomized rats, a beta(2)-agonist (procaterol), and a nonspecific beta-antagonist (propranolol) indicate that overexpression maximally up-regulates beta(2)-adrenergic-responsive alveolar fluid clearance and improves responsiveness to endogenous catecholamines. Mechanistic studies in human lung epithelial cells (A549) indicate that receptor overexpression prevents homologous receptor desensitization, possibly by overwhelming endogenous regulatory pathways. Our studies demonstrate that overexpression of beta(2)AR in lung epithelial cells can be used to study the role and regulation of alveolar beta(2)ARs. They also suggest a therapeutic role for the beta(2)AR in the treatment of pulmonary edema.

Animals↗