Bradykinin causes hypotension by activating pulmonary sympathetic afferents in the rabbit

Abstract

causes hypotension by activating pulmonary sympathetic afferents in the rabbit. J Appl Physiol 95: 233-240, 2003. First published April 4, 2003 10.1152/japplphysiol.00584.2002 activates sympathetic afferents in the heart, intestine, and kidney, and it alters hemodynamics. However, we know little about the influence of pulmonary sympathetic afferents on circulation. Activation of pulmonary afferents by directly injecting stimulants into the lung parenchyma permits examination of reflexes that originate in the lung without confounding effects from the systemic circulation. In the present study, we tested the hypothesis that pulmonary sympathetic afferents exert a significant influence on hemodynamics. We examined reflex effects of injecting BK (1 g/kg in 0.1 ml) into the lung parenchyma on circulation in anesthetized, open-chest, artificially ventilated rabbits. BK significantly decreased mean arterial blood pressure (BP) (27 Ϯ 3 mmHg) and heart rate (19 Ϯ 4 beats/min). Both effects remained after bilateral vagotomy. To rule out possible direct systemic vasodilation by BK, we examined renal sympathetic nerve activity (RSNA) in response to BK injection and examined BP responses to injection of ACh (0.1 ml of 10 Ϫ4 M). BK suppressed the RSNA before and after vagotomy. ACh did not change BP when injected into the lung parenchyma, but it decreased BP (31 Ϯ 3 mmHg) when injected into the right atrium. Our data indicate that activating pulmonary sympathetic afferents reflexly suppresses hemodynamics. lung receptors; lung reflex; depressor effect; bradycardia FOR DECADES IT HAS BEEN RECOGNIZED that cardiovascular regulation is strongly influenced by inputs from the lung (24). These pulmonary inputs are believed to travel mainly in the vagus nerves. Mechanically activating pulmonary stretch receptors (33) or chemically activating pulmonary C fibers (4) in the vagus nerve can cause peripheral vasodilation and changes in heart rate. Activation of some pulmonary vagal afferents in the rabbit causes a slight pressor response in addition to stimulating breathing (25, 34). However, information regarding the reflex effects evoked from pulmonary sympathetic afferents is scarce and debatable (23).Sensory information in the lung is transmitted through vagal and sympathetic nerves (32). Morphological evidence points to the existence of sympathetic afferents in the lungs (13,18,22). Pulmonary sympathetic afferent activity has been recorded in stellate ganglia (9) and white rami of T 2

Characterization of thoracic spinal neurons with noxious convergent inputs from heart and lower airways in rats

“…For example, injecting bradykinin, as inflammatory mediator, into the lung parenchyma after bilateral vagotomy in rabbits still evokes significant cardiovascular and respiratory responses, i.e. hyperpnea, tachypnea and hypotension Wang et al 2003). Irritation of the lungs or release of chemicals during myocardial ischemia in heart might activate spinal (sympathetic) afferents and excite thoracic cardiopulmonary convergent spinal neurons.…”

“…For example, a characteristic cardiopulmonary reflex (hyperpnea, tachypnea and hypotension) is elicited by stimulation of pulmonary sympathetic afferents with intrapulmonary bradykinin Wang et al 2003). Dramatic responses in the cardiovascular and respiratory systems to noxious stimuli of heart and lungs also may relate to some pathological conditions.…”

A case of acute respiratory distress syndrome responsive to methylene blue during a carcinoid crisis

“…2 In animal models, bradykinin causes increased pulmonary vascular permeability, vasodilation, and hypotension. [4][5][6] These actions may be mediated in part through the activation of nitric oxide synthase. 9,10 Methylene blue competitively inhibits the binding of nitric oxide to soluble guanylate cyclase, thereby preventing the downstream activation of cyclic guanosine monophosphate and smooth muscle relaxation.…”

“…3 Importantly, bradykinin has been shown to increase pulmonary vascular permeability and produce hypotension in animals; however, little is known about pharmacologically modifying its effects in a carcinoid crisis. [4][5][6] Herein, we report a severe case of postoperative carcinoid crisis associated with acute respiratory distress syndrome (ARDS) that was refractory to conventional antiserotonin and antihistamine therapies. A rapid improvement in oxygenation and blood pressure was observed following administration of methylene blue, suggesting that methylene blue may be an adjunct treatment for shock and non-cardiogenic pulmonary edema associated with a carcinoid crisis.…”

Effects of Proximal Pulmonary Artery Occlusion on Pulsatile Right Ventricular Afterload in Rats

“…We estimated PA impedance using irregular pacing and employed a method of unilateral proximal PA occlusion rather than unilateral pneumonectomy to acutely reduce pulmonary perfusion volume. As afferent signals from the lung are known to exert reflex effects on autonomic nervous activities and hemodynamics, 24 proximal PA occlusion may mimic acute PTE better than pneumonectomy in that the afferent signals from the occluded lung might have been preserved.…”