Effect of sublingual nitrate on respiratory reflexes arising from stimulation of juxta-pulmonary capillary (J) receptors by i.v. lobeline and short duration exercise

Juxta-pulmonary capillary (J or pulmonary C fiber) receptors are stimulated by an increase in pulmonary blood flow and give rise to respiratory acceleration and related sensations and inhibit exercise. However, the reverse, i.e., the effect of reducing pulmonary blood flow on their reflexes, is as yet not known. This was investigated by carrying out a placebo-controlled study on the acute effects of a single dose (0.4 mg) of sublingual glyceryl nitrate (GTN), known to shift blood from the central to the peripheral circulation, on the respiratory parameters of exercising healthy subjects and on their responses to i.v. lobeline.In 10 subjects, GTN use delayed the first appearance of respiratory sensations from 9.08 ± 0.9 min to 11 min (P = 0.002), reduced the increase in minute ventilation by the end of 10 min of exercise (P = 0.003) and increased its duration by 1–4 s and doubled it in the remaining one subject. In a majority of 8 of them, the effect of GTN on i.v. lobeline-induced respiratory reflexes and sensations was a significant increase in the dose required (P = 0.006) for producing threshold effects and in the latency of their appearance (P = 0.003). The latter feature points to a reduction in blood flow in the lung parenchyma where these receptors are located and to which they are sensitive. As this would have led to a reduced stimulation of these receptors, it would account for the delayed appearance of respiratory symptoms, a reduction in ventilatory increase and prolongation of exercise duration.We demonstrated a mechanism of reducing the stimulus level of J receptors by reducing pulmonary blood flow by means of pharmacological sequestration with GTN use, which then led to a reduction in the magnitude of respiratory and viscerosomatic reflexes, while noting at the same time that changes in blood flow in the pulmonary bed do not directly influence limb muscles, tendons and joints which also determine exercise output.

► Reduction in natural stimulus of J receptors was attempted in healthy subjects by pharmacological venosequestration using sublingual nitrate.
► Respiratory acceleration and sensations with i.v. lobeline, delayed and reduced.
► Exercise duration increased, minute ventilation-increase reduced and appearance of dyspnoea delayed.
► These responses demonstrate slowing of blood flow in lung parenchyma and reduced J receptor stimulation.
► The above responses were not seen after sublingual placebo.