Rapidly adapting receptors in a rabbit model of mitral regurgitation

Abstract

Pulmonary rapidly adapting receptors (RARs) in anaesthetized intact rabbits are activated by small changes in the extravascular fluid spaces of the major airways where they are located (Hargreaves et al. 1991). It has also been shown that stimulation of RARs in this manner causes reflex increases in respiratory rate (Kappagoda et al. 1989), tracheal tone (Kappagoda et al. 1988) and mucus production by the respiratory epithelium (Yu et al. 1989). All these reflex effects collectively form the syndrome of cardiac asthma which is characterized by wheezing, an increased respiratory rate and increased mucus production. Therefore, it was suggested that in chronic left ventricular dysfunction, intermittent, small acute elevations of left atrial pressure (LAP) cause these exacerbations in symptoms through activation of RARs (Hargreaves et al. 1991). However, in a recent study from our laboratory performed on rabbits maintained in a state of chronic pulmonary venous congestion (PVC) secondary to surgically induced mitral regurgitation (MR), acute small elevations (+10 mmHg) of LAP failed to activate RARs (Gunawardena et al. 1998). It was speculated that in these animals this lack of response of RARs could be due to a change either in the receptor per se, or in the extravascular space surrounding the receptor. These issues were addressed in the present study by testing the following hypotheses: (i) shrinking the extravascular space by an intravenous infusion of hypertonic albumin restores the sensitivity of previously insensitive RARs (to small, acute elevations of LAP) in rabbits with chronic PVC, (ii) the increase in extravascular fluid volume in major airways resulting from small elevations of LAP is less in animals with chronic PVC than in age-matched control animals, and (iii) enhancing the stimulus to RARs by increasing the LAP above 25 mmHg stimulates previously insensitive RARs in rabbits with chronic PVC. As in the 1. Unlike in normal rabbits, pulmonary rapidly adapting receptors (RARs) in rabbits with chronic mitral regurgitation (MR) do not respond to small changes in extravascular fluid (EVF) volume in major airways. The present study examined the effect of shrinking the EVF volume in rabbits with chronic MR by infusing hypertonic albumin, to see whether this response of RARs is restored. The effect of raising the left atrial pressure (LAP) acutely above 25 mmHg (to cause pulmonary oedema) on RARs was also investigated. 2. Mean RAR activities in rabbits with MR (n = 6) at initial control, LAP +5 mmHg, LAP +10 mmHg and final control periods were 20·9 ± 9·5, 18·8 ± 11·3, 27·0 ± 11·2 and 17·2 ± 9·8 action potentials min¢, respectively (P > 0·05, ANOVA). After infusion of 35% bovine serum albumin i.v. these values were 9·4 ± 3·2, 30·6 ± 14·6, 48·9 ± 10·1 and 18·4 ± 7·3 action potentials min¢, respectively (P < 0·01, ANOVA). In rabbits with chronic MR (n = 7) raising the LAP above 25 mmHg stimulated RARs. 3. EVF content of the airways and lungs was measured in rabbits with MR and in control rabbits, at baseline and...

The characteristics of a porcine mitral regurgitation model

“…Organic MR model: Animal MR models are an important tool for cardiovascular research and can be implemented in large mammals, such as pigs [ 1 , 14 ], dogs [ 26 , 38 ], sheep [ 16 , 34 ], as well as in small mammals, such as rabbits [ 11 ], rats [ 15 , 27 ], among others. The rat MR model is produced via by thoracotomy.…”

The rapidly adapting receptors in mammalian airways and their responses to changes in extravascular fluid volume

“…The extravascular fluid in the carina and proximal bronchi increases when the LAP is raised by 10 mmHg. The data were obtained from Gunawardena et al (1999, 2002). * P < 0.05 significantly increased from control values.…”

“…in the carina and proximal bronchi. Simultaneously, it was possible to show that there was no increase in extravascular fluid in the alveoli until the left atrial pressure was in excess of 25 mmHg (Gunawardena et al 1998, 1999, 2002). These findings are summarized in Table 1.…”

Role of nitric oxide in the reflex diuresis in rabbits during pulmonary lymphatic obstruction

“…A pair of bipolar platinum electrodes was used to record single unit activity of pulmonary RARs from these nerve filaments. The details of the procedures for identifying and recording action potentials from RARs have been described previously (Gunawardena et al 1999). Action potentials arising from RARs were identified by their burst of activity and rapid adaptation (over 70% adaptation in 1 s) to a sustained inflation of the lungs with three tidal volumes of air.…”