Hypertonicity activates pulmonary vagal afferents independently of vasoconstriction

Abstract

Injecting hypertonic saline into the lung periphery causes a vagally mediated neural hyperpnea and tachypnea (the excitatory lung reflex, ELR). In the present study, we tested the hypothesis that hypertonic saline activates lung afferents mainly by increasing fluid flux from pulmonary vessels into the alveoli. If our hypothesis is correct, reducing perfusion of the vagal sensory region will reduce the fluid flux and attenuate the ELR. In anesthetized, open chest and mechanically ventilated rabbits, using intravital video microscopy, we confirmed that topical KCl (100 mM) constricted sub-pleural blood vessels and limited blood flow significantly, as indicated by a 43.3±9% decrease in arteriolar diameters (p<0.005), sluggish microvascular flow and paleness of alveolar walls. Then, we compared respiratory responses (assessed from phrenic nerve activity) to injections of hypertonic saline (8.1%, 0.1 ml) into the lung periphery before and after locally injecting KCl to limit fluid flux. The respiratory responses were the same with or without vasoconstriction. However, the responses were significantly decreased (from 22±5% to 1±2% for phrenic amplitude and from 75±9% to 13±6% for phrenic burst rate; n=14, p<0.02) after local injection of 2% lidocaine to block sensory endings. Since the ELR was not attenuated by vasoconstriction, increased transvascular fluid flux does not appear to be a major mechanism for hypertonic saline induced ELR.