Bradykinin B2 receptors mediate pulmonary sympathetic afferents induced reflexes in rabbits

Endogenous bradykinin (BK) is an established mediator of pulmonary inflammation, yet its role in lung disease is unclear. In the rabbit, injecting BK into the lung parenchyma elicits reflex hyperpnea, tachypnea, hypotension, and bradycardia by stimulating pulmonary sympathetic afferents. To further explore bradykinin effects, breathing pattern (phrenic nerve and abdominal muscle activities) and hemodynamics (blood pressure and heart rate) were examined in anesthetized, open-chest, and mechanically ventilated rabbits. Three receptor agonists [bradykinin, selective B(1) (des-Arg(9)-BK), and selective B(2) (Tyr(8)-BK)], as well as three B(2) receptor antagonists, B6029 (N alpha-Adamantaneacetyl)-Bradykinin, B(1)650 (D-Arg-[Hyp(3), Thi(5,8), D-Phe(7)]-Bradykinin, or Hoe-140 (D-Arg-[Hyp(3), Thi(5), D-Tic(7), Oic(8)] bradykinin), were used to identify the responsible receptor subtype. In both intact and vagotomized rabbits, injecting BK or a selective B(2) agonist into the lung elicited similar cardiopulmonary responses. These reflex responses were greatly attenuated or blocked by pre-injecting B(2) antagonists into the right atrium or into the lung parenchyma. In contrast, the B(1) agonist elicited fewer cardiopulmonary effects in intact rabbits and had no effect in vagotomized rabbits. We conclude that BK stimulates pulmonary sympathetic afferents [Soukhova, G., Wang, Y., Ahmed, M., Walker, J., Yu, J., 2003. Bradykinin stimulates respiratory drive by activating pulmonary sympathetic afferents in the rabbit. J. Appl. Physiol. 95, 241-249.; Wang, Y., Soukhova, G., Proctor, M., Walker, J., Yu, J., 2003. Bradykinin causes hypotension by activating pulmonary sympathetic afferents in the rabbit. J. Appl. Physiol. 95, 233-240.], eliciting a characteristic cardiopulmonary reflex via B(2) receptors.