Function of the rat carotid body chemoreceptors in ageing

Abstract

Some age-related deficits in the ventilatory responses have been attributed to a decline in the functionality of the carotid body (CB) arterial chemoreceptors, but a systematic study of the CB function in ageing is lacking. In rats aged 3-24 months, we have performed quantitative morphometry on specific chemoreceptor tissue, assessed the function of chemoreceptor cells by measuring the content, synthesis and release of catecholamines (a chemoreceptor cell neurotransmitter) in normoxia and hypoxia, and determined the functional activity of the intact organ by measuring chemosensory activity in the carotid sinus nerve (CSN) in normoxia, hypoxia and hypercapnic acidosis. We found that with age CBs enlarge, but at the same time there is a concomitant decrease in the percentage of chemoreceptor tissue. CB content and turnover time for their catecholamines increase with age. Hypoxic stimulation of chemoreceptor cells elicits a smaller release of catecholamines in rats after 12 months of age, but a non-specific depolarizing stimulus elicits a comparable release at all ages. In parallel, there was a marked decrease in the responsiveness to hypoxia, but not to an acidic-hypercapnic stimulus, assessed as chemosensory activity in the CSN. We conclude that in aged mammals chemoreceptor cells become hypofunctional, leading to a decreased peripheral drive of ventilation.

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

“…The finding that changes in cAMP content at the CB in response to O 2 concentrations did not change with aging, suggests that the compensatory mechanism could occur within the CB as a whole. These results contrast with the reduction in carotid sinus nerve discharges in response to hypoxia observed in old rats (Conde et al 2006). It is known that the glossopharyngeal nerve has, in addition to carotid sinus nerve afferent fibers, a parallel autonomic parasympathetic efferent pathway sensitive to hypoxia that is the source of CB inhibition (Campanucci et al 2006).…”

“…There is a consensual body of evidence about the changes in the morphology of the CB throughout aging: increase in extracellular matrix, reduction in number and volume of type I cells, and in the volume and density of mitochondria compared with young CB (Hurst et al 1985;Pokorski et al 2004;Conde et al 2006). These morphological findings do not apparently concur with the absence of functional impairment.…”

“…It is known that the glossopharyngeal nerve has, in addition to carotid sinus nerve afferent fibers, a parallel autonomic parasympathetic efferent pathway sensitive to hypoxia that is the source of CB inhibition (Campanucci et al 2006). We can speculate that the reduction in CSN discharges found in old animals (Conde et al 2006) could mainly be due to an impairment of the efferent fiber activity without changes in the chemosensory excitatory afferent pathway. Similarly, it was shown in humans that aging impairs the autonomic responses to pain but does not modify nociceptive perception (Hajduczok et al 1991).…”

“…It is known that aging causes marked changes in the morphology of the CBs (Hurst et al 1985) and reduces catecholamine release and CSN output in response to hypoxia in rat isolated CBs (Conde et al 2006). In contrast, it has been suggested that peripheral chemoreceptor activity in healthy humans is not impaired by aging (Smith et al 2001;Pokorski et al 2004).…”

Differences in tyrosine hydroxylase expression after short-term hypoxia, hypercapnia or hypercapnic hypoxia in rat carotid body

“…Therefore, it is suggested that the expression of TH mRNA returns to the control level after a sufficient amount of TH protein is secured. Conde et al (2006) reported that 280 dopamine content was increased by exposure to hypoxia in rat CB. Welsh et al (1978) suggested that dopamine suppressed ventilation through action of the CB.…”