Effect of bradykinin on respiratory rate in anaesthetized rabbits; role of rapidly adapting receptors.

1. This study was performed in anaesthetized, spontaneously breathing rabbits: (a) to determine the effect of bradykinin administered into the right atrium on the respiratory rate, and (b) to elucidate the potential role of rapidly adapting receptors (RARs) in mediating this effect. The role of RARs was established by graded cooling of the cervical vagi. The respiratory rate was measured from an intrapleural pressure tracing. 2. Dose-response curves relating right atrial injections of bradykinin (0.25, 0.5, 1.0 and 1.5 micrograms/kg) to the respiratory rate were established in the control state (i.e. vagi at 37 degrees C). The respiratory rate increased significantly (P < 0.01, ANOVA) from a control value of 51.3 +/- 6.8 breaths/min by 12 +/- 3, 25 +/- 5, 43 +/- 7 and 58 +/- 11% respectively. At doses of 1.0 and 1.5 micrograms/kg I.V., the increase in rate was preceded by apnoea. 3. The dose-response curves were repeated with bolus injections of bradykinin (0.25, 0.5, 1.0 and 1.5 micrograms/kg) after cooling the cervical vagi to 8-9 degrees C. The increase in respiratory rate was attenuated significantly (P < 0.01 ANOVA). The rate increased from a control value of 27.2 +/- 2.1 breaths/min by 5 +/- 2, 6 +/- 2, 16 +/- 5 and 21 +/- 8% respectively. With vagi cooled, apnoea was increased in duration and occurred at lower doses. On rewarming vagi, the original responses were reestablished. 4. When the study was repeated after bilateral vagotomy, apnoea was abolished but there was a small residual increase in rate. This increase was similar to that seen after cooling the vagi (P > 0.05). 5. RAR (n = 5) activity was recorded from the cervical vagus. Right atrial injections of bradykinin (0.25-1.0 micrograms/kg) stimulated RARs. On cooling the vagi to 8-9 degrees C caudal to the recording site, the increase in activity was blocked. 6. These data support the proposition that bradykinin increases the respiratory rate in rabbits and that this response is, in part, a reflex mediated by RARs. In addition, bradykinin has other secondary effects on respiration: an aponea which is mediated by non-myelinated vagal afferents and a small stimulatory effect on respiration which persists after bilateral vagotomy.