TY - JOUR
T1 - Cyclooxygenase inhibition prevents PMA-induced increase in pulmonary vascular permeability to albumin
AU - Zanaboni, P. B.
AU - Bradley, J. D.
AU - Webster, R. O.
AU - Dahms, T. E.
PY - 1992
Y1 - 1992
N2 - In a previous study, we demonstrated that phorbol myristate acetate-(PMA) induced injury in isolated blood-perfused rabbit lungs was characterized by increased pulmonary vascular resistance (PVR) and permeability to water as measured by fluid filtration coefficient (K(f)). The K(f) increase was prevented by pretreatment with three cyclooxygenase inhibitors, indomethacin, ibuprofen, and meclofenamate. Other studies have shown that PMA causes a decrease in pulmonary vascular surface area, probably due to the increase in arterial resistance. Measurement of K(f) requires increased microvascular pressure, and therefore K(f) estimates the permeability of the entire vascular bed. Thus the permeability of the flowing vessels may be overestimated by K(f). In this study, we chose to investigate the effect of PMA on vascular permeability to protein by measuring albumin leak. Because this measurement does not require a hydraulic stress, it is more likely to reflect the permeability of flowing vessels. PMA administration (5 x 10-8 M) caused significant increases in both PVR and 125I-labeled bovine serum albumin leak. Cyclooxygenase inhibition with indomethacin, ibuprofen, or meclofenamate prevented the PMA-induced increase in albumin leak without affecting the PVR increase. These results suggest that cyclooxygenase- mediated products of arachidonic acid mediate the PMA-induced increase in vascular permeability to both water and protein.
AB - In a previous study, we demonstrated that phorbol myristate acetate-(PMA) induced injury in isolated blood-perfused rabbit lungs was characterized by increased pulmonary vascular resistance (PVR) and permeability to water as measured by fluid filtration coefficient (K(f)). The K(f) increase was prevented by pretreatment with three cyclooxygenase inhibitors, indomethacin, ibuprofen, and meclofenamate. Other studies have shown that PMA causes a decrease in pulmonary vascular surface area, probably due to the increase in arterial resistance. Measurement of K(f) requires increased microvascular pressure, and therefore K(f) estimates the permeability of the entire vascular bed. Thus the permeability of the flowing vessels may be overestimated by K(f). In this study, we chose to investigate the effect of PMA on vascular permeability to protein by measuring albumin leak. Because this measurement does not require a hydraulic stress, it is more likely to reflect the permeability of flowing vessels. PMA administration (5 x 10-8 M) caused significant increases in both PVR and 125I-labeled bovine serum albumin leak. Cyclooxygenase inhibition with indomethacin, ibuprofen, or meclofenamate prevented the PMA-induced increase in albumin leak without affecting the PVR increase. These results suggest that cyclooxygenase- mediated products of arachidonic acid mediate the PMA-induced increase in vascular permeability to both water and protein.
KW - albumin leak
KW - fluid filtration coefficient
KW - permeability
KW - prostaglandins
UR - http://www.scopus.com/inward/record.url?scp=0026471242&partnerID=8YFLogxK
U2 - 10.1152/jappl.1992.73.5.2011
DO - 10.1152/jappl.1992.73.5.2011
M3 - Article
C2 - 1474079
AN - SCOPUS:0026471242
SN - 0161-7567
VL - 73
SP - 2011
EP - 2015
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 5
ER -