Journal of Applied Physiology, Vol 62, Issue 2 599-605, Copyright © 1987 by American Physiological Society
Parasympathetic involvement in PAF-induced contraction in canine trachealis in vivo
A. R. Leff, S. R. White, N. M. Munoz, K. J. Popovich, T. Shioya and N. P. Stimler-Gerard
We studied the contractile response elicited by platelet-activating factor
(PAF) administered intra-arterially into the tracheal circulation of 34
dogs in vivo. A method that avoided tachyphylaxis encountered in prior
investigations was developed for isometric measurement of multiple
dose-response effects. PAF was a very potent contractile agent; active
tension was elicited with 10(-11) mol ia PAF. To determine the mechanism by
which contraction was induced, dose-response curves were generated in
groups of five animals each treated with either 0.5 mg/kg (approximately
1.5 X 10(-5) mol) iv + 10(-3) mg/kg (3 X 10(-8) mol) ia atropine, 5 mg/kg
iv indomethacin (INDO), or 7.5 mg/kg iv hexamethonium (HEX). After
pretreatment with atropine, contraction still was elicited with 10(-11) mol
ia PAF. However, maximal contraction was only 16.2 +/- 2.74 g/cm (vs. 35.7
+/- 5.74 g/cm for untreated controls; P less than 0.02). The dose at which
maximal contraction was elicited after atropine was 10(-7) mol ia (vs. 1.9
X 10(-9) mol for controls; P less than 0.001). Pretreatment with INDO
caused minimal attenuation, and HEX had no effect on the response elicited
by ia PAF. We demonstrate a method for assessing the effects of PAF in
central airways that avoids tachyphylaxis and permits dose-response studies
in the same animal. We also demonstrate that PAF is an extremely potent
mediator that elicits tracheal smooth muscle contraction at least in part
by postganglionic activation of parasympathetic nerves. A direct
contractile effect of PAF which is not related to secretion of products of
the cyclooxygenase pathway is also suggested.
