Bradykinin-Induced Excitation of Afferent Cardiac Sympathetic Nerve Fiber

Abstract

SUMMARYThe effect of bradykinin on afferent cardiac sympathetic nerve fibers has been examined. Using anesthetized dogs, the action potentials of the fi bers were derived from either the 2nd or 3rd thoracic communicating ramus of the left side. Excitation of the afferent fibers was observed following administration of bradykinin acetate dissolved in physiological saline on the left ventricular wall. The minimum concentration required for excitation was 50-100ng/ml. The fibers were excited rhythmically synchronous with myocardial contraction and/or relaxation. However, no significant augmentation of myocardial contraction was produced by the agent. Bradykinin-induced excitation of the fibers was significantly reduced by pretreatment with acetylsalicylic acid. The results suggest bradykinininduced sensitization of the receptor sites of the afferent fibers for normal modality of left ventricular motion. 2) This substance is the most powerful of all the algesic agents.3) It causes pain in humans when it is applied to a blister base on the skin or when injected into somatic and visceral arteries4)-7) and elicites the pseudaffective response in animals when injected into the coronary artery.1) However, it is unclear whether this agent activates the afferent cardiac sympathetic nerve fibers which subserve nociception of the heart.8)-10) Our studies have been undertaken to examine the effect of bradykinin acetate solutions on afferent sympathetic nerve fibers which originated in the left ventricular wall.

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

“…Tachyphylaxis has been found to develop in cutaneous mechanoreceptors in cats when bradykinin is administered at 15 min intervals (Beck & Handwerker, 1974). The development of tachyphylaxis to bradykinin was not observed in previous studies of cardiac sympathetic mechanoreceptors (Uchida & Murao, 1974a;Nichi et al 1977), however, and the excitatory nociceptive reflex described by Staszewska-Barczak et al (1976) (1978) found that previous application of low concentrations of prostaglandin El prevented the development of tachyphylaxis when bradykinin was applied to sympathetic afferent endings in the heart, and when a cardiac receptor had become desensitized by repeated applications of bradykinin application of prostaglandin E1 to the receptor site restored the bradykinin response to its initial level. A similar interaction between bradykinin and prostaglandin E has been demonstrated in experiments on cutaneous nociceptors (Handwerker, 1976), and this type of interaction may explain the potentiation observed in reflex experiments.…”

“…We usually applied bradykinin to the tissues in a solution containing 1 #g/ml. because this concentration applied to the epicardium produces the maximum reflex increase in blood pressure (Staszewska-Barezak et al 1976) and also the maximum stimulation of cardiac sympathetic afferent nerves (Uchida & Murao, 1974a). Topical application of bradykinin (1 0 #g/ml.)…”

“…Sympathetic afferent pathways appear to be solely responsible for signalling the pain of myocardial ischaemia (Sutton & Lueth, 1930;Lindgren & Olivecrona, 1947;White, 1957). Local application of low concentrations of bradykinin to the epicardium of anaesthetized dogs has been found to excite sympathetic afferent fibres with endings in the left ventricle (Uchida & Murao, 1974a) and to evoke a pseudo-affective reflex increase in arterial blood pressure and heart rate (Staszewska-Barczak et al 1976). …”

“…The nerve endings so far found to be stimulated by bradykinin, however, appear to belong to the first, rather than the second category. Thus, Uchida & Murao (1974a) reported that the ventricular nerve endings excited by bradykinin fired in time with the cardiac cycle, and they postulated that bradykinin sensitized these mechanosensitive endings to their normal stimulus, which was provided by the rhythmical mechanical changes in the ventricular wall. Nishi, Sakanashi & Takenaka (1977) confirmed that bradykinin increased the firing of mechanosensitive endings in the ventricle; they also showed that the endings were supplied by myelinated fibres.…”

Cardiovascular actions of rattlesnake bradykinin ([Val1,Thr6]bradykinin) in the anesthetized South American rattlesnakeCrotalus durissus terrificus

“…However, in mammals and pythons, injection of BK leads to a rise in circulating catecholamines, which is released from sympathetic neurons (27,28).…”