Phosphodiesterase 4 inhibition attenuates plasma volume loss and transvascular exchange in volume-expanded mice

Yueh Chen Lin, Roger H. Adamson, Joyce F. Clark, Rolf K. Reed, Fitz Roy E Curry

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

We tested the hypothesis that inhibition of phosphodiesterase 4 (PDE4) with rolipram to increase vascular endothelial cAMP and stabilize the endothelial barrier would attenuate the action of endogenous atrial natriuretic peptide (ANP) to increase vascular permeability to the plasma protein albumin after an acute plasma volume expansion. After rolipram pretreatment (8 mg (kg body wt) -1, intraperitoneal, 30 min) more than 95% of the peak increase in plasma volume after volume expansion (4.5% bovine serum albumin, 114 μl (g body wt) -1 h -1, 15 min) remained in the vascular space 75 min after the end of infusion, whereas only 67% of the fluid was retained in volume-expanded animals with no rolipram pretreatment. Rolipram significantly decreased 30 min fluorescently labelled albumin clearance (μl (g dry wt) -1) relative to untreated volume-expanded controls in skin (e.g. back, 10.4 ± 1.6vs. 19.5 ± 3.6,P= 0.04), muscle (e.g. hamstring, 15.0 ± 1.9vs.20.8 ± 1.4,P= 0.04) and in colon, caecum, and rectum (average reduction close to 50%). The mass of muscle and skin tissue accounted for 70% of volume-expansion-dependent albumin shifts from plasma to interstitium. The results are consistent with observations that the PDE4 inhibitor rolipram attenuates ANP-induced increases in vascular permeability after infusion of exogenous ANP and observations of elevated central venous pressure after a similar volume expansion in mice with selective deletion of the endothelial ANP receptor. These observations may form the basis for new strategies to retain intravenous fluid containing macromolecules.

Original languageEnglish (US)
Pages (from-to)309-322
Number of pages14
JournalJournal of Physiology
Volume590
Issue number2
DOIs
StatePublished - Jan 2012

ASJC Scopus subject areas

  • Physiology

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