Passage of aerosolized BSA and the nona-peptide dDAVP via the respiratory tract in young and adult rats.
The passage of the protein marker, bovine serum albumin (BSA, MW = 67,000), and the nona-peptide, 1-deaminocysteine-8-D-arginine vasopressin (dDAVP, MW = 1067), from the respiratory tract into the blood when applied as an aerosol with a MMAD of 1.7 microns was studied in 14-, 30-, and 100-120-day-old (adult) healthy rats and in adult rats with lung injury. In blood serum of adult rats the levels of immunoreactive BSA reached its maximum 16-24 h after a 1-h aerosol exposure with a calculated total passage of 6.4 +/- 1.8% of the given dose. dDAVP serum levels measured by RIA peaked after 0.5-1 h, giving a total passage of 84.3 +/- 12.9%. With increasing exposure periods from 0.5 to 3 h, which thereby increased the lung burden, the serum levels of BSA and dDAVP increased linearly indicating passive transepithelial transport processes for both molecules. For the young rats, similar serum level-time curves were obtained like those of the adult, with similar total passages of BSA, 4.6 +/- 0.8% for the 14-day-old rats and 5.2 +/- 1.6% for the 30-day-old rats. For dDAVP the total passage was significantly lower in both the 14-day-old rats, 40.9 +/- 12.1%, and the 30-day-old rats, 16.7 +/- 6.1% (p less than .05), as compared to the adult rats. Acute lung inflammation induced in rats by intratracheal instillation of 5 mg ferritin/kg body wt prior to a 1-h marker aerosol exposure increased the passage of BSA (58.7 +/- 18.8%, p less than .05), while the dDAVP passage was less affected (99.2 +/- 25.2%, p greater than .05) as compared to the healthy adult rats. The results indicate that after aerosol exposure the total passage of dDAVP over the respiratory tract was higher than that of the macromolecule BSA, the passage appeared to increase with the maturity of the rats and by inflammatory changes in the lung tissue.
Folkesson
H G
HG
Department of Animal Physiology, University of Lund, Sweden.
Weström
B R
BR
Dahlbäck
M
M
Lundin
S
S
Karlsson
B W
BW
D000336:Aerosols; D000367:Age Factors; D000818:Animals; D003894:Deamino Arginine Vasopressin / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008168:Lung / Q000378:metabolism*; D008297:Male; D011014:Pneumonia / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*
D000336:Aerosols; D012710:Serum Albumin, Bovine; D003894:Deamino Arginine Vasopressin