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

Abstract

SUMMARY1. Veratridine injected into the coronary circulation stimulates afferent vagal endings in the heart to evoke bradycardia and systemic hypotension (Bezold-Jarisch reflex, coronary chemoreflex) and coronary vasodilatation. We have examined certain features of the reflex coronary vasodilator response in anaesthetized dogs.2. When the circumflex coronary artery was perfused at constant pressure (100 mmHg), injection of veratridine (03 Ig kg-1) into the anterior descending artery decreased blood pressure and heart rate, and increased circumflex blood flow by 54 %; when heart rate was kept constant, circumflex flow increased by 57 %. The increase in circumflex flow was reduced 63 % by atropine, and finally abolished by phentolamine. 3. During severe coronary underperfusion (perfusion pressure 45 mmHg), veratridine still increased coronary flow by 35 %, an increase amounting to 24-64 % of the coronary vascular reserve. Flow increased in all layers of the myocardium, but the relative distribution of flow between subendocardial and subepicardial layers was unaltered.4. Veratridine stimulates both mechanosensitive and chemosensitive cardiac endings. Stimulating chemosensitive afferents selectively by injecting capsaicin (1V5 jug kg-') into the anterior descending artery decreased blood pressure and heart rate, and increased circumflex flow by 50 % (and by 36 % when heart rate was kept constant).5. In ten of fifteen dogs, veratridine and capsaicin still evoked coronary vasodilatation when vagal A fibres were blocked selectively by cooling to 7 5°C, the increase in coronary flow averaging 45 % of that at 37 'C. All responses were abolished by cooling to 0 'C.6. We conclude that coronary vasodilatation can be evoked by selective stimulation of cardiac chemosensitive vagal C fibres, although the coronary vasodilatation of the veratridine-induced Bezold-Jarisch reflex may be due to stimulation of both mechanosensitive and chemosensitive C fibres. We speculate that during periods of coronary underperfusion ischaemic stimulation of chemosensitive vagal C fibres evokes a reflex dilatation of the coronary vascular bed that supplements the dilatation dependent upon autoregulatory mechanisms. MUS 8253 J. P. CLOZEL AND OTHERS

Regulation of Coronary Blood Flow

“…Although data from Duncker et al indicate that the withdrawal of parasympathetic activity may facilitate β-adrenoceptor dilation in swine during exercise (280), the effects of the parasympathetic nervous system on the control of coronary blood flow are quite modest under most physiologic conditions (198, 280, 332, 335). However, there is evidence to support a role for parasympathetic coronary vasodilation in the carotid chemoreceptor reflex (430,442,700,703,950), Bezold-Jarisch reflex (186,330,1027), and during activation of afferent vagal C fibers in the lung (187, 734). …”

Reflex effects on the coronary circulation

“…Injection of the chemical agents caused a reflex increase in coronary blood flow and myocardial blood flow to all layers of the ventricular wall, and involved afferent non-myelinated vagal fibres. In contrast to the findings of Zucker et al (1987), the efferent pathways were shown by the use of atropine and phentolamine to involve both vagal and sympathetic effects (Clozel et al 1990). The differences between the two reports may be attributed to a greater efferent sympathetic activity in anaesthetized animals since the response entailed withdrawal of this activity.…”

“…More recently, this reflex was re-examined in anaesthetized dogs in which veratridine or capsaicin was injected into the left anterior descending artery (Clozel, Pisarri, Coleridge & Coleridge, 1990). Responses of blood flow were measured by an electromagnetic flowmeter probe in the left circumflex coronary artery which was perfused by arterial blood at constant pressure through a cannula wedged into this coronary artery.…”

Pharmacology of vagal afferent influences on disordered breathing during sleep

“…Carley and coworkers further demonstrated that two other pharmacologic activators of vagal afferents, capsaicin (Hedner et al 1985) and protoveratrine (Clozel et al 1990) also increased spontaneous SRBD in rats (Trbovic et al 1997; Carley et al 2004). Interestingly, unlike serotonin, capsaicin, which activates primarily c-fibers, and protoveratrine, which stimulates free nerve endings, increased apnea expression only during NREM sleep (Figs.…”