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Phosphodiesterase 4 inhibition attenuates plasma volume loss and transvascular exchange in volume‐expanded mice
Author(s) -
Lin YuehChen,
Adamson Roger H.,
Clark Joyce F.,
Reed Rolf K.,
Curry FitzRoy E.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.213447
Subject(s) - medicine , endocrinology , rolipram , albumin , chemistry , intravascular volume status , atrial natriuretic peptide , phosphodiesterase inhibitor , phosphodiesterase , hemodynamics , enzyme , biochemistry
Non‐technical summary When vascular volume is expanded, atrial natriuretic peptide (ANP) released from the heart acts to restore plasma volume by increasing renal water excretion, causing vasodilatation and increasing vascular permeability to water and macromolecules. Previous experiments using mice with selective deletion of ANP receptors in vascular endothelial cells emphasized the importance of vascular permeability regulation by ANP in plasma volume restoration because this genetic manipulation of ANP action on vascular permeability limited the restoration of vascular volume after an acute increase in plasma volume. Here we demonstrate retention of intravenously infused fluid in wild‐type mice in which the response to endogenous ANP was attenuated by the pharmacological agent rolipram that stabilized the endothelial barrier by tightening adhesion between adjacent endothelial cells. The strategy may provide novel approaches to the clinical problem of maintenance of vascular volume after acute intravenous fluid infusion.