Participation of the kallikrein‐kinin‐receptor system in reflexes arising from neural afferents in the dog epicardium.

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Abstract
1. Reflexogenic effects of bradykinin, lysyl‐bradykinin and endogenously formed kinins on neural afferents of the left ventricular epicardium were studied in anaesthetized, open‐chest dogs. 2. Epicardial application of either bradykinin (0.01‐10 micrograms), lysyl‐bradykinin (0.01‐10 micrograms) or tissue kallikrein (0.003‐1 U) consistently resulted in dose‐related increases in blood pressure and heart rate. The pressor and heart rate responses to epicardial kallikrein were slower in onset and longer lasting than those evoked by bradykinin or lysyl‐bradykinin. The effects of kallikrein, but not those of exogenous kinins, were subject to tachyphylaxis. The application of higher doses of kallikrein (0.1 or 1 U) also resulted in long‐lasting desensitization of the epicardium to the effects of bradykinin. 3. Treatment of the epicardium with a proteinase inhibitor, aprotinin, prevented the reflexogenic effects of kallikrein but not those of bradykinin or lysyl‐bradykinin. Treatment with aprotinin also counteracted post‐kallikrein desensitization of sensory receptors of the ventricular epicardium to the reflexogenic effect of bradykinin. 4. Superfusion of the epicardium with a selective B2 receptor antagonist, D‐Arg[Hyp3,Thi5,8,D‐Phe7]‐bradykinin, was equally effective in antagonizing the reflexogenic effects of kallikrein, bradykinin and lysyl‐bradykinin. 5. We conclude that the response to epicardial application of kallikrein indicates an ample presence of endogenous substrate for local formation of bradykinin and/or related kinins. These then initiate reflex activation of the cardiovascular system by interacting with specific B2 receptors associated with sympathetic afferent neurones in the dog epicardium. We suggest that the kallikrein‐kinin‐receptor system has a role in the reflex function of the cardiac sympathetic afferents in both physiological and pathological conditions.