Search for a cardiac nociceptor: stimulation by bradykinin of sympathetic afferent nerve endings in the heart of the cat.

Abstract

SUMMARY1. We have examined the effect of bradykinin on impulse traffic in sympathetic afferent fibres from the heart, great vessels and pleura, and have attempted to identify cardiac nociceptors that on the basis of their functional characteristics might have a role in the initiation of cardiac pain.2. In anaesthetized cats, we recorded afferent impulses from 'single-fibre' slips of the left 2nd-5th thoracic rami communicantes and associated chain, and selected fibres arising from endings in the heart, great vessels, pericardium and pleura. We applied bradykinin solution (0 1-1.0 jug/ml.) locally to the site of the ending; we also injected bradykinin (0 3-1 0 ,ug/kg) into the left atrium.3. Afferent endings excited by bradykinin (158 of 191 tested) were of two types. The larger group (140) were primarily mechanoreceptors with Ad or C fibres (mean conduction velocity, 7-5 + 0-6 m/sec). They were very sensitive to light touch. Those located in the heart, great vessels or overlying pleura had a cardiac rhythm of discharge and were stimulated by an increase in blood pressure or cardiac volume.4. Bradykinin increased mechanoreceptor firing from 0 7 + 0.1 to 5 0 + 0 3 (mean + S.E. of mean) impulses/sec. Some endings appeared to be stimulated directly by bradykinin, others sensitized by it so that they responded more vigorously to the pulsatile mechanical stimulation associated with the cardiac cycle.5. The smaller group of eighteen endings, of which ten were in the left ventricle, were primarily chemosensitive. Most had C fibres, a few had A6 fibres (mean conduction velocity, 2-3 + 0-7 m/sec). They were insensitive to light touch. With one exception they never fired with a cardiac rhythm, and even large increases in aortic or left ventricular pressure had little effect on impulse frequency. 6. Chemosensitive endings were stimulated by bradykinin, impulse activity increasing from 0.6 + 0-2 to 15-6 + 1-3 impulses/sec and remaining above the control level for 1-3 min. The evoked discharge, which was either continuous or occurred in irregular bursts, was not secondary to mechanical changes in the heart and great vessels.

From the Cover: Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons

“…There is conflicting literature about adenosine action on cardiac afferents, with some groups supporting a role in cardiac pain (37)(38)(39) and others not (40,41). Bradykinin increases firing of cardiac afferents in vivo (40,42) by acting at B 2 receptors (43). It is cleaved from kininogens by the enzyme kallikrein, which can be triggered by a drop in pH.…”

Bradykinin causes hypotension by activating pulmonary sympathetic afferents in the rabbit

“…In addition, it is possible to deliver a high concentration of stimulants to pulmonary afferents without directly entering the circulation. In several respects, the use of local injection to study reflexes from pulmonary afferents is similar to topical application of stimulants in studying other organs, such as the heart (3,20) and abdominal-visceral organs (8). The concentration of bradykinin used in the present study is comparable to that reported in the topical application to the heart [from 1 g/ml (3,20) to 10-100 g/ml (30)] and to the gut [10 g/ml (8)].…”

“…Because the injections were into the most peripheral lung, no obvious blood vessels were encountered. Bradykinin produces tachyphylaxis in cardiac receptors (3); therefore, at least 15 min elapsed between injections. To further determine whether the observed responses were related to activation of pulmonary afferents, rather than originating from the systemic vasculature, in separate trials in six rabbits we compared the hypotensive effects of acetylcholine (0.1 ml of 10 Ϫ4 M) when it was directly injected into the lung and into the right atrium.…”

Neural control of sympathetic nerve response to cardiogenic hypotension in anesthetized cat.

“…Thus, a possible contribution of chemical substances released by coronary occlusion to excite the cardiac afferents cannot be excluded from the present study. Previous studies also suggested that the sympathetic afferent nerves may transmit the sensation of pain during myocardial ischemia to the central nervous system (WHITE, 1957;BAKER et a!.,1980;BLAIR et a!., 1982). Thus, further experiments are required to evaluate the net autonomic response to cardiogenic hypotension determining the central interactions of input from cardiac sympathetic afferents and from arterial baroreceptors and cardiac vagal afferents, and to determine more exact interaction with impaired cardiac function and cardiac sympathetic afferents during the hypotension induced by coronary occlusion.…”

“…However, the nature of the stimulus to cardiac receptors was not investigated in the present study. The efferent sympathetic excitatory responses to coronary occlusion may have been initiated by chemical NEURAL RESPONSE TO CARDIAC ISCHEMIA 521 substances such as bradykinin or potassium (REIMANN and WEAVER, 1980;BAKER et al, 1980), as well as mechanical stimuli to the heart. Thus, a possible contribution of chemical substances released by coronary occlusion to excite the cardiac afferents cannot be excluded from the present study.…”