Cardiovascular reflexes mediated by capsaicin sensitive cardiac afferent neurones in the dog

Abstract

Reflex circulatory changes mediated by capsaicin sensitive cardiac afferent neurones were studied in anaesthetised, open chest dogs. Application of capsaicin to the epicardium of the left ventricle, either in single doses (0.01-100 micrograms) or by superfusion (20 micrograms X min-1), consistently resulted in dose related increases in blood pressure and heart rate. These responses were not affected by bilateral vagotomy but were abolished or reversed by bilateral sectioning of the upper thoracic (T1-T4) white rami communicantes and stellectomy. Injection of capsaicin (0.3-1 microgram X kg-1) into the left circumflex coronary artery caused either systemic hypotension and bradycardia (70.3% of experiments), a pressor response associated with tachycardia (13.5%), or a biphasic effect with an initial rise and then fall in blood pressure and heart rate (16.2%). With intravenous injections of capsaicin (3-5 micrograms X kg-1) the response was invariably cardioinhibitory and depressor. The reflex bradycardia and hypotension evoked with either intracoronary or intravenous injections of capsaicin were reversed after bilateral vagotomy to increases in cardiac rate and blood pressure. The post-vagotomy tachycardia occurring with intracoronary capsaicin could be abolished by beta adrenoceptor blockade with propranolol (0.5 mg X kg-1 iv), whereas ganglionic transmission blockade with pentolinium (0.5 mg X kg-1 iv) eliminated both the tachycardia and pressor effects. The results indicate that in the dog's heart capsaicin sensitive afferent neurones capable of affecting the circulatory system have both vagal and spinal sympathetic origin. It is suggested that capsaicin induced excitatory cardiogenic reflex is nociceptive in nature and may involve activation of substance P containing afferent fibres incorporated in cardiac sympathetic nerves.

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

“…A depletion of brain kininogen has been implicated in the desensitization of rabbit pial arterioles to the second dose of kallikrein, since the arterioles still responded normally to exogenous bradykinin (Kamitani, Little & Ellis, 1985). In the present experiments, tachyphylaxis to kallikrein was associated with a long-lasting (up to 60 min) reduction of reflexogenic effects of exogenous kinins, but not that of capsaicin which also involves activation of cardiac afferents incorporated in spinal thoracic sympathetic nerves (Staszewska-Woolley et al 1986). Since treatment of the epicardium with the proteinase inhibitor, aprotinin, counteracted kallikrein-induced desensitization to bradykinin, occupation of neural receptor sites by endogenously formed kinins could be responsible for the development of tachyphylaxis to both kallikrein and exogenous kinins.…”

“…Solutions of drugs were maintained at room temperature and were applied to the epicardium in a volume of 1 ml over a period of 2-3 s. Successive epicardial applications of bradykinin and lysyl-ENDOGEN.OUfS KIXINS AND CARDL4C REFLEXES bradykinin were separated by intervals of 5-10 min and were usuallv alternate(l. Initervals between consecutive epicardial applications of kallikrein depended on the dose and ranged from 10-20 min for lower doses (0-003-001 U) and from 30-90 min for higher doses (0 1-1 U). An interval of at least 20 min was maintained between consecutive applications of capsaicin (Staszewska-Woolley, Luk & Nolan. 1986).…”

“…Kallikrein (from porcine pancreas, Sigma), containing 22 U (mg solid)-', was dissolved in distilled water to produce a stock solution of 10 U mnl-' further dilutions were made in normal saline. (Capsaicin (Sigma) was dissolved using two drops of 'Tween 80' (BDH Chemicals) and ethyl alcohol to make a 10 mg ml-' stock solution (Staszewska-Woolley et al 1986). An aliquot was removed and diluted in saline to make a 10 jug ml-' solution which was further diluted with saline.…”

Reflex coronary vasodilation evoked by chemical stimulation of cardiac afferent vagal C fibres in dogs.

“…were responsiblebecause both are stimulated by veratridine. However, only chemosensitive endings are stimulated by capsaicin (Coleridge et al 1964;Baker et al 1979;Kaufman et al 1980), and results of injecting capsaicin into the coronary artery indicate that these afferents by themselves are capable of evoking coronary vasodilatation (present results), as well as bradycardia and systemic hypotension (Staszewska-WAoolley, Luk & Nolan, 1986;present results).…”

Effects of neuropeptides, ruthenium red and neuraminidase on chemoreflexes mediated by afferents in the dog epicardium.

“…Electrophysiological and reflex studies conducted on dogs or cats established the ability of bradykinin and capsaicin to excite both vagal (Coleridge, Coleridge & Kidd, 1964;Kaufman, Baker, Coleridge & Coleridge, 1980) and spinal sympathetic afferents with endings in the heart (Uchida & Murao, 1974;Baker, Coleridge, Coleridge & Nerdrum, 1980;Bolser. Chandler, Garrison & Foreman, 1989) and thereby initiate either inhibitory (Neto, Brasil & Antonio, 1974;Staszewska-Woolley, Luk & Nolan, 1986) or excitatory reflex cardiovascular changes (Staszewska-Barezak, Ferreira & Vane, 1976;Weaver, Meckler, Fry & Donoghue, 1983;Staszewska-Woolley et al 1986). The neuropeptide SP has already been found to be without any reflexogenic effect on either vagal or sympathetic afferents in the dog heart (Staszewska-Woolley et al 1986). The present study was concerned with assessing whether other neuropeptides contained in cardiac sensory nerves, specifically CGRP and neurokinins, can activate directly and/or influence the responsiveness of neural afferents in the dog epicardium to the reflexogenic actions of bradykinin, capsaicin and nicotine.…”