Vasopressin-2 receptor antagonist attenuates the ability of the lungs to clear edema in an experimental model.
In the last two decades, the role of the alveolar active sodium transport was extensively studied and was found to play a crucial role in regulating alveolar fluid clearance (AFC), and thus in keeping the airspaces free of edema. The recent development of highly selective nonpeptide vasopressin-receptor antagonists gives us a rare chance to explore the role of vasopressin in the pathogenesis of lung edema. Therefore, the present study examined the involvement of vasopressin in modulating the ability of the lung to clear edema. Vasopressin enhanced the rate of lung edema clearance by 30% as compared with untreated control rats (from 0.49 ± 0.02 to 0.64 ± 0.02 ml/h), whereas V(2) receptor antagonists significantly decreased the ability of the lung to clear water (from 0.64 ± 0.02 to 0.31 ± 0.06 ml/h; P < 0.0001). In contrast, V(1) receptor antagonist did not change the rate of AFC. The administration of ouabain (a Na,K-ATPase inhibitor) and amiloride (a Na(+) channel blocker) inhibited the stimulatory effects of vasopressin (from 0.64 ± 0.02 to 0.22 ± 0.02 ml/h [P < 0.0001] and from 0.64 ± 0.017 to 0.23 ± 0.02 ml/h [P < 0.0001], respectively). Vasopressin significantly increased Na,K-ATPase protein abundance in the basolateral membranes of the alveolar epithelial cells via V(2) receptor activation. We report a novel role of the vasopressin pathway in AFC. This observation indicates a beneficial role of vasopressin in AFC by up-regulating active sodium transport.
Dept. of Internal Medicine B, Rambam Health Care Campus, P.O. Box 9602, Haifa, 31096 Israel.
Julia
J
Guetta
Geula
G
Klorin
Ronit
R
Tal
Gidon
G
Berger
Reem
R
Ismael-Badarneh
Bishara
B
Bishara
Edmond
E
Sabo
Zaid
Z
Abassi
Zaher S
ZS
Azzam
D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010539:Permeability; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011654:Pulmonary Edema / Q000378:metabolism* / Q000503:physiopathology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000819:agonists / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013141:Spiro Compounds / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology / Q000502:physiology
D065092:Antidiuretic Hormone Receptor Antagonists; D007211:Indoles; D009025:Morpholines; D011759:Pyrrolidines; D017483:Receptors, Vasopressin; D013141:Spiro Compounds; D014667:Vasopressins; D010042:Ouabain; D000584:Amiloride; C103281:satavaptan; C082134:relcovaptan; D000254:Sodium-Potassium-Exchanging ATPase; D003078:Colchicine