Analysis of the pressor sympathetic reflex produced by intracoronary injections of bradykinin in conscious dogs

Abstract

The reflex hemodynamic effects of intracoronary bradykinin were tested in 20 conscious instrumented dogs. When the experiments were performed after full recovery from surgery and anesthesia, graded doses (10-300 ng/kg) of bradykinin always produced graded pressor responses, in the absence of any pain reaction. At the maximum pressor response obtained with 100 ng/kg, mean arterial pressure rose 28 ± 3% from 89 ± 4 mm Hg, left ventricular pressure 20 ± 3% from 121 + 2 mm Hg, heart rate 30 ± 4% from 88 ± 5 beats/min, rate of change of left ventricular pressure 18 ± 3% from 2812 ± 65 mm Hg/sec (P < 0.01). Higher doses of bradykinin did not produce greater responses. The magnitude of the response was similar when the injection was performed in either the left anterior descending (change in mean arterial pressure 29 ± 3%) or circumflex (change in mean arterial pressure 27 ± 2%) coronary artery. The reflex nature of the response was proved by its disappearance after appropriate pharmacological blockades; moreover, after vagotomy, the pressor rise was maintained, the heart rate response was reduced (change in heart rate 10 ± 2%), and the inotropic response was enhanced (rate of change of left ventricular pressure 24 ± 3%). This suggested that the afferent pathway of the pressor reflex was in the sympathetic nerves and that a subordinate vagal depressor reflex was also operative. No pain reaction was obtained even when injecting very large amounts (1000-2000 ng/kg) of bradykinin, which, instead, induced arterial hypotension. Pain reactions (as inferred by agitation and vocalization) were observed in three out of nine dogs studied during the first week after surgery. This reaction was no longer present when the same animals were tested later on, at the time of complete recovery. In five of the nine dogs studied during the first week after surgery, the intracoronary injection of bradykinin produced a depressor (change in mean arterial pressure -31 ± 6%) response, which, however, reverted to a pressor effect (change in mean arterial pressure 22 ± 4%) later, when recovery was complete. In five additional dogs, the pressor response observed after full recovery from surgery was no longer present when the injection of bradykinin was repeated under anesthesia. The present experiments in conscious dogs show that the chemical stimulation of the fully innervated heart with intracoronary bradykinin can initiate pressor reflexes independent of pain and in the presence of intact buffering mechanisms.