Hemorrhagic hypotension-induced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats

Abstract

Lin RL, Lin YJ, Xu F, Lee LY. Hemorrhagic hypotensioninduced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats. Am J Physiol Regul Integr Comp Physiol 308: R605-R613, 2015. First published January 14, 2015 doi:10.1152/ajpregu.00424.2014.-This study was carried out to investigate whether hemorrhagic hypotension (HH) altered the sensitivity of vagal pulmonary C-fibers. The fiber activity (FA) of single vagal pulmonary C-fiber was continuously recorded in anesthetized rats before, during, and after HH was induced by bleeding from the femoral arterial catheter into a blood reservoir and lowering the mean systemic arterial pressure (MSAP) to ϳ40 mmHg for 20 min. Our results showed the following. First, after MSAP reached a steady state of HH, the peak FA response to intravenous injection of capsaicin was elevated by approximately fivefold. The enhanced C-fiber sensitivity continued to increase during HH and sustained even after MSAP returned to baseline during the recovery, but slowly returned to control ϳ20 min later. Second, responses of FA to intravenous injections of other chemical stimulants of pulmonary C-fibers (phenylbiguanide, lactic acid, and adenosine) and a constantpressure lung hyperinflation were all significantly potentiated by HH. Third, infusion of sodium bicarbonate alleviated the systemic acidosis during HH, and it also attenuated, but did not completely prevent, the HH-induced C-fiber hypersensitivity. In conclusion, the pulmonary C-fiber sensitivity was elevated during HH, probably caused by the endogenous release of chemical substances (e.g., lactic acid) that were produced by tissue ischemia during HH. This enhanced C-fiber sensitivity may heighten the pulmonary protective reflexes mediated through these afferents (e.g., cough, J reflex) during hemorrhage when the body is more susceptible to other hazardous insults and pathophysiological stresses.hemorrhage; pulmonary; C-fiber; hypoxia; hypersensitivity VAGAL BRONCHOPULMONARY C-fibers represent ϳ75% of the vagal afferents arising from the lung and airways (17). These unmyelinated afferents innervate the entire respiratory tract and play an important role in regulating the respiratory functions under various physiological and pathophysiological conditions (5, 21). Activation of these afferents elicits centrally mediated protective reflex responses via the cholinergic pathway, which include laryngeal closure, bronchoconstriction and airway hypersecretion, accompanied by cough, airway irritation, dyspneic sensation, and J reflex (5, 21). Activation of these sensory nerves can also trigger release of tachykinins and calcitonin gene-related peptide from the sensory terminals, which can act on a number of effector cells in the respiratory tract (e.g., smooth muscles, cholinergic ganglia, mucous glands, immune cells), and elicit the local "axon reflexes" such as bronchoconstriction, protein extravasation, and inflammatory cell chemotaxis (5, 18, 21).Tissue ischemia is known to activate C-fib...

Modulation of Neurally Mediated Vasodepression and Bradycardia by Electroacupuncture through Opioids in Nucleus Tractus Solitarius

“…The current study underscores the importance of opioids in the NTS and the potential of acupuncture at specific acupoints to minimize the vasodepression and bradycardia responses induced by vagal activation. Parasympathetic activation underlies many hypotensive responses, for instance those occurring during alveolar hemorrhage, hypercapnia and vasovagal syncope 25 , 26 , 47 . Excitation of vagal pulmonary C-fibers in response to hemorrhage, chemical stimuli such as CO 2, capsaicin and PBG profoundly decreases BP and HR that potentially can be modulated by EA 4 , 9 , 25 , 26 , 47 , 48 .…”

“…Parasympathetic activation underlies many hypotensive responses, for instance those occurring during alveolar hemorrhage, hypercapnia and vasovagal syncope 25 , 26 , 47 . Excitation of vagal pulmonary C-fibers in response to hemorrhage, chemical stimuli such as CO 2, capsaicin and PBG profoundly decreases BP and HR that potentially can be modulated by EA 4 , 9 , 25 , 26 , 47 , 48 . Of note, EA-inhibition does not influence baseline BP and HR 16 , 49 – 51 , suggesting that EA does not influence tonic autonomic output or hemodynamic stability.…”

“…Reflex vasodepression and bradycardia evoked by activation of cervical and abdominal vagal afferents are mediated by parasympathetic pathways 4 , 24 . More specifically, decreases of BP and HR are induced by stimulation of pulmonary vagal C-fibers with adenosine, capsaicin, hypercapnia, hemorrhage or phenylbiguanide (PBG) 25 – 27 . Similar to its actions on reflex sympathoexcitatory responses, EA at P5–6 acupoints also reduces parasympathoexcitatory reflex responses, i.e.…”

Neurogenic Hypotension and Bradycardia Modulated by Electroacupuncture in Hypothalamic Paraventricular Nucleus

“…Many hypotensive responses, for instance, those occurring during alveolar hemorrhage, hypercapnia, and vasovagal syncope, employ the parasympathetic system ( Kaufmann, 1995 ; Gu and Lee, 2002 ; Lin et al, 2015 ). Activation of vagal pulmonary C-fibers induced by hemorrhage, chemical stimuli, such as CO 2 , capsaicin, and PBG, results in a profound reduction of blood pressure and heart rate that likely can be modulated by acupuncture, such as EA ( Kaufmann, 1995 ; Gu and Lee, 2002 ; Syuu et al, 2003 ; Tjen-A-Looi et al, 2012 , 2013 ; Lin et al, 2015 ).…”

“…Many hypotensive responses, for instance, those occurring during alveolar hemorrhage, hypercapnia, and vasovagal syncope, employ the parasympathetic system ( Kaufmann, 1995 ; Gu and Lee, 2002 ; Lin et al, 2015 ). Activation of vagal pulmonary C-fibers induced by hemorrhage, chemical stimuli, such as CO 2 , capsaicin, and PBG, results in a profound reduction of blood pressure and heart rate that likely can be modulated by acupuncture, such as EA ( Kaufmann, 1995 ; Gu and Lee, 2002 ; Syuu et al, 2003 ; Tjen-A-Looi et al, 2012 , 2013 ; Lin et al, 2015 ). Importantly, inhibitory actions of EA do not influence baseline blood pressure and heart rate ( Li et al, 1998 , 2002 , 2004 ; Tjen-A-Looi et al, 2007 ), implying that EA does not influence basal tone of autonomic output associated with hemodynamic stability.…”