EFFECT OF BRADYKININ ON RESPIRATORY RATE IN ANESTHETIZED 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 t he right atrium on the respiratory rate, and (b) to elucidate the pote ntial role of rapidly adapting receptors (RARs) in mediating this effe ct. 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 mug/kg) to the respiratory rate wer e established in the control state (i.e. vagi at 37-degrees-C). The re spiratory rate increased significantly (P < 0.01, ANOVA) from a contro l value of 51.3 +/- 6.8 breaths/min by 12 +/- 3, 25 +/- 5, 43 +/- 7 an d 58 +/- 11% respectively. At doses of 1.0 and 1.5 mug/kg i. v., the i ncrease in rate was preceded by apnoea. 3. The dose-response curves we re repeated with bolus injections of bradykinin (0.25, 0.5, 1.0 and 1. 5 mug/kg) after cooling the cervical vagi to 8-9-degrees-C. The increa se 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 coole d, apnoea was increased in duration and occurred at lower doses. On re warming vagi, the original responses were reestablished. 4. When the s tudy was repeated after bilateral vagotomy, apnoea was abolished but t here 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) activit y was recorded from the cervical vagus. Right atrial injections of bra dykinin (0.25-1.0 mug/kg) stimulated RARs. On cooling the vagi to 8-9- degrees-C caudal to the recording site, the increase in activity was b locked. 6. These data support the proposition that bradykinin increase s 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 apnoea which is mediated by non-myelinated vagal afferents and a small stimulatory effect on respiration which p ersists after bilateral vagotomy.