Parasympathetic involvement in PAF-induced contraction in canine trachealis in vivo

Abstract

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.

Regulatory pathways for the stimulation of canine tracheal ciliary beat frequency by bradykinin.

“…In vivo, these cyclooxygenase products may stimulate the afferent pathway of a cholinergic parasympathetic reflex. This hypothesis appears to be supported by our findings on the presumptions that hexamethonium bromide is a specific ganglionic blocker which inhibits the efferent (postganglionic) transmissions (Leff, White, Munoz, Popovich, Shioya & Stimler-Gerard, 1987) and that ipratropium bromide is a specific muscarinic antagonist which inhibits the effects of 'acetylcholine' released at the neuroepithelial junction.…”

Role of the Cholinergic Pathway in Mediating Platelet‐Activating Factor‐induced Pulmonary Dysfunctions in Unsedated Calves

“…The present data show that acetylcholine release contributes to the PAF bronchoconstrictor response, as evidenced by the antagonistic properties 110 VAN DE WEERDT et al of atropine. These findings support results of studies in which atropine was reported to antagonize the effects of PAF in tracheal muscle of dogs (LEFF et al, 1987). Likewise, MUNOZ et al (1991) have demonstrated that PAF has a direct contractile effect on both the central and the peripheral airways of rats and that PAF causes substantial augmentation of muscarinic responsiveness in rat pulmonary airways (BETHEL et al, 1989;MUNOZ et al, 1991).…”

5‐Hydroxytryptamine‐induced bronchoconstriction in the guinea‐pig: effect of 5‐HT2 receptor activation on acetylcholine release

“…In the dog and rabbit, parasympathetic activation within the airways was recently demonstrated to play a significant role in the airway responses to other bronchoconstrictor agents, e.g. histamine, platelet activating factor (PAF) and substance P (Shore et al, 1985;Leff et al, 1987;Grunstein et al, 1984). As regards PAF and substance P, parasympathetic activation within the airways appears to be the sole contribution of the parasympathetic system to their bronchoconstrictor effects.…”