AJP - Lung Cellular and Molecular Physiology, Vol 260, Issue 4 260-L267, Copyright © 1991 by American Physiological Society
Effects of PAF on isolated rat airways perfused with blood-free solution
N. M. Munoz, C. F. Kirchhoff, M. E. Strek, R. N. Blumenthal and A. R. Leff
Department of Medicine, University of Chicago, Illinois 60637.
We examined the mechanism of constriction and muscarinic augmentation of
contraction of airway smooth muscle caused by platelet-activating factor
(PAF) in airways from 55 Sprague-Dawley rats perfused through the isolated
bronchial circulation (BC) and pulmonary circulation (PC) and isometrically
in tissue perfusion chambers. Dose-response curves were generated
cumulatively by infusing 10(-10) to 10(-7) mol PAF dissolved in
Krebs-Henseleit solution buffer containing 4% bovine serum albumin into the
BC or PC. The efficacy of PAF in central airways (BC) was approximately
twofold greater in increasing lung resistance (RL) than for more peripheral
airways perfused by the PC (P less than 0.05). Tachyphylaxis was
demonstrated in both BC and PC for preparations in which a second PAF
dose-response curve was generated. Bolus injection of 10(-6) mol of the PAF
antagonist, CV-6209, plus 10(-7) mol PAF caused 81% reversal of the maximal
BC response. The same dose of CV-6209 reversed the response to PAF in the
PC by 99.2%. Initial administration of 10(-6) mol CV-6209 with PAF
prevented completely contraction elicited by PAF in the BC and PC.
Concentration-response studies also were generated isometrically in tissue
perfusion chambers from 64 tracheal smooth muscle strips. Maximal
contraction elicited by 10(-6) M PAF was blocked completely with 10(-6) M
CV-6209. In separate studies, addition of 10(-6) mol CV-6209 to the BC
perfusate caused 93% blockade of the RL response to PAF and 100% inhibition
when administered in the PC. Prior administration of PAF caused two- to
fourfold augmentation of the contractile response to acetylcholine (ACh)
within the same preparation; in the presence of CV-6209, the response to
ACh was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
