Biomedical subjects

Y R Kou

Publications and source records attributed to Y R Kou.

44 records · Page 3Linked to original sources

PubMed1991

Mechanisms of cigarette smoke-induced stimulation of rapidly adapting receptors in canine lungs.

The stimulation of rapidly adapting receptors (RARs) in the lungs evoked by cigarette smoke consists of an initial and either a type I or a type II delayed response (Kou and Lee, J. Appl. Physiol. 68: 1203, 1990). In the type I response, receptor activity increased during expirations and exhibited a prominent cardiac modulation, whereas in the type II response, receptor discharge reached its peak during inspiration at peak transpulmonary pressure. To investigate the mechanisms of this stimulation, we recorded the vagal afferent activity arising from 39 RARs and delivered a single breath (120 ml) of cigarette smoke in 15 anesthetized, open-chest and artificially ventilated dogs. Studies were repeated after a pretreatment with aerosolized hexamethonium (3-8 breaths, 10%), aerosolized isoproterenol (12-15 breaths, 2%), or after the cardiac impact on the lung had been minimized by elevating the apex of the heart. The initial response of RARs was totally abolished by hexamethonium but was not affected by isoproterenol. The increase of total lung resistance induced by cigarette smoke and the concomitant type II delayed response of RARs were both abolished by isoproterenol. The type I delayed response of RARs was eliminated or largely attenuated after the apex of the heart had been elevated. Based upon these results, we conclude that a direct effect of nicotine on these receptors may be responsible for the immediate stimulation while the systemic effects of absorbed nicotine may play a part in evoking the delayed stimulation.

Adaptation, Physiological↗

PubMed1990

Stimulation of rapidly adapting receptors in canine lungs by a single breath of cigarette smoke.

Inhalation of smoke generated from high-nicotine cigarettes frequently evoked an immediate augmented inspiration in conscious dogs (J. Appl. Physiol. 54: 562-570, 1983); this reflex response was believed to result from a stimulation of rapidly adapting receptors in the lungs. To test this hypothesis, we recorded the vagal afferent activity arising from the rapidly adapting receptors in the lungs and delivered 120 ml of high- and low-nicotine cigarette smoke separately in a single ventilatory cycle in 20 anesthetized open-chest and artificially ventilated dogs. These receptors were stimulated on the first breath of delivery of smoke generated by high-nicotine cigarettes; activity increased from a base line of 0.9 +/- 0.2 to a peak of 9.9 +/- 1.2 (SE) impulses/breath (n = 58). After three to six breaths when the receptors' discharge returned toward base-line activity, a delayed increase of activity emerged (peak activity = 3.4 +/- 0.6 impulses/breath, n = 58) in 32 of the 58 receptors studied and lasted for three to seven breaths. By contrast, only a mild stimulatory effect of low-nicotine cigarette smoke was found, either immediately or after a delay, in 15 of the 54 receptors studied. We conclude that rapidly adapting receptors are stimulated by a single breath of cigarette smoke and that nicotine is the primary stimulant agent.

Adaptation, Physiological↗

PubMed1990

Acute effects of cigarette smoke on breathing in rats: vagal and nonvagal mechanisms.

The acute ventilatory response to inhalation of cigarette smoke was studied in anesthetized Sprague-Dawley rats. Cigarette smoke (6 ml, 50%) generated by a machine was inhaled spontaneously via a tracheal cannula. Within the first two breaths of smoke inhalation, a slowing of respiration resulting from a prolonged expiratory duration (173 +/- 6% of the base line; n = 32) was elicited in 88% of the rats studied. This initial inhibitory effect on breathing was not affected either by an increase (410%) in the nicotine content of the cigarette smoke or by pretreatment with hexamethonium (33 mg/kg iv). However, bilateral vagotomy completely eliminated the initial ventilatory inhibition. Cooling both vagi to 5.1 degrees C blocked the reflex apneic response to lung inflation, but it did not abolish the inhibitory effect of smoke. After the initial response, a rapid shallow breathing pattern developed and reached its peak 5-12 breaths after inhalation of high-nicotine cigarette smoke; this delayed response could not be prevented by vagotomy and was undetectable after inhalation of low-nicotine smoke. We conclude that the initial inhibitory effect of smoke on breathing is mediated by vagal bronchopulmonary C-fiber afferents, which are stimulated by smoke constituents other than nicotine, whereas the delayed tachypneic response to smoke is caused by the absorbed nicotine.

Animals↗

PubMed1989

The stimulatory effect of nicotine on vagal pulmonary C-fibers in dogs.

Our recent studies suggested that a nicotine-induced stimulation of afferent vagal C-fibers in the lungs was involved in eliciting the immediate cardiorespiratory responses to inhaling cigarette smoke. To examine this possibility, afferent impulses were recorded from vagal pulmonary C-fibers in 16 anesthetized, open-chest and artificially ventilated dogs, before and after four separate doses of nicotine (2.5, 5, 10 and 20 micrograms/kg) were injected into the right atrium. The base-line activity did not change after injection of isotonic saline. In contrast, nicotine stimulated 24 of 29 C-fibers: a burst of discharge was evoked immediately (1-2 sec) after the injection and usually lasted 3-8 sec. The peak responses of these pulmonary C-fibers to nicotine injections showed a dose-dependent relationship. In 17 C-fibers tested, the responses evoked by right atrial injection of 10 micrograms/kg of nicotine were similar to those evoked by delivery into the lungs of a single breath of smoke generated from cigarette with a high-nicotine content. Based upon these results, we conclude that nicotine alone stimulates vagal pulmonary C-fibers in a dose-dependent manner and this stimulant action of nicotine may play a part in eliciting the immediate reflex cardiorespiratory responses to inhalation of cigarette smoke.

Afferent Pathways↗

PubMed1989

Stimulation of vagal pulmonary C-fibers by a single breath of cigarette smoke in dogs.

Inhalation of cigarette smoke into the lower airway via a tracheostomy evokes immediate apnea, bradycardia, and systemic hypotension in dogs. These responses can still be evoked when conduction in myelinated vagal fibers is blocked preferentially by cooling but are abolished by vagotomy, suggesting that they are mediated by afferent vagal C-fibers. To examine this possibility, we recorded impulses in pulmonary C-fibers in anesthetized, open-chest dogs and delivered 120 ml cigarette smoke to the lungs in a single ventilatory cycle. Pulmonary C-fibers were stimulated within 1 or 2 s of the delivery of smoke generated by high-nicotine cigarettes, activity increasing from 0.3 +/- 0.1 to a peak of 12.6 +/- 1.3 (SE) impulses/s, (n = 60); the evoked discharge usually lasted 3-5 s. Smoke generated by low-nicotine cigarettes evoked a milder stimulation in 33% of pulmonary C-fibers but did not significantly affect the overall firing frequency (peak activity = 2.2 +/- 1.1 impulses/s, n = 36). Hexamethonium (0.7-1.2 mg/kg iv) prevented C-fiber stimulation by high-nicotine cigarette smoke (n = 12) but not stimulation by right atrial injection of capsaicin. We conclude that pulmonary C-fibers are stimulated by a single breath of cigarette smoke and that nicotine is the constituent responsible.

Action Potentials↗

PubMed1987

Role of bronchopulmonary C-fiber afferents in the apneic response to cigarette smoke.

The role of vagal bronchopulmonary C-fiber afferents in eliciting the immediate changes in breathing pattern after acute inhalation of cigarette smoke was assessed with a selective blockade of myelinated vagal afferents (innervating both stretch and irritant receptors) utilizing the method of differential cooling. In 15 of 17 chloralose-anesthetized dogs tested, spontaneous inhalation of cigarette smoke (19.7% avg conc, 500-700 ml vol) reproducibly caused the following immediate responses: apnea, bradycardia, and hypotension. These responses occurred within 1 to 2 breaths of smoke inhalation and were followed by a delayed hyperpnea. The apneic duration reached 326 +/- 33% (SE) (n = 15) of the mean base-line expiratory duration. Differential cold block of both vagi (coolant temperature 8.4 +/- 0.3 degrees C) abolished the reflex apnea induced by a positive-pressure (7-10 cmH2O) lung inflation but did not affect the apneic response to smoke inhalation (345 +/- 35%). The smoke-induced apnea was completely abolished by lowering the coolant temperature to -1.3 +/- 0.2 degrees C (n = 10) or by bilateral vagotomy (n = 5) and returned to the control level after both vagi were rewarmed. Based on these results, we suggest that the immediate apneic response to inhaled cigarette smoke is elicited by a stimulation of vagal C-fiber afferents in the lungs and airways.

Afferent Pathways↗

PubMedDate not supplied

Effect of a single breath of cigarette smoke on slowly adapting receptors in canine lungs.

Inhalation of cigarette smoke has been shown to induce bronchoconstriction which should stimulate slowly adapting pulmonary stretch receptors (PSRs). To test this possibility, the activity of PSRs was recorded from fine afferent filaments of the vagus nerve before and after 120 ml of smoke generated from high-nicotine cigarettes was delivered into the lungs in a single breath in anesthetized, open-chest and artificially ventilated dogs. The base-line activity of PSRs did not change during the first two breaths following smoke delivery. However, PSR activity started to increase by the third breath (post-smoke), concomitant with an increase in tracheal (transpulmonary) pressure. Both the smoke-induced increase in tracheal pressure and the delayed effect on PSRs were prevented by a pretreatment with aerosolized isoproterenol, a bronchodilator, suggesting that the delayed response of PSRs to smoke was elicited by the change in bronchomotor tone. Although smoke evoked a delayed stimulation in the majority (61%) of the PSRs studied, it caused a mild delayed inhibition (24%) or had no effect (15%) in some of the receptors. The variable responses to smoke among PSRs are probably related to the smoke-induced heterogeneous changes of mechanical properties in the lungs and their different anatomic locations.

Action Potentials↗

PubMedDate not supplied

G proteins in carotid body chemoreception.

G proteins are signal coupling molecules that play major roles in mediating the effects of transmitters as well as certain sensory signals. In the present study we examined whether oxygen chemoreception in the carotid body is coupled to G proteins. Experiments were performed on carotid bodies isolated from anesthetized cats. Presence of G proteins was examined with ADP-ribosylation of the carotid body membranes. Pertussis toxin (PTX), which inactivates G proteins in neuronal tissues, ADP-ribosylated a single band of carotid body protein with a molecular mass of 41 kDa. With cholera toxin (CTX) only a faint band of protein corresponding to approximately 45 kDa was evident. Perfusing the isolated carotid bodies with PTX (2.5 micrograms/min; 60 min) attenuated the sensory response to hypoxia by 52% of the controls. Perfusion with CTX (50 micrograms/min; for 60 min), on the other hand, increased baseline activity and potentiated the hypoxic response by 125% of controls. Heat-inactivated toxins, however, had no influence on the carotid body sensory response to hypoxia. These results suggest that G proteins are present in the chemoreceptor tissue and they seem to be coupled to the transduction and/or to the transmission of the hypoxic stimulus.

Animals↗