Original ArticlesEffect of Chronic Hyperoxia on Young and Old Rat Carotid Body Ultrastructure
Introduction
The aging process is characterized by a decline in several physiological functions. During postnatal development, the carotid body (CB) undergoes several morphologic, physiological and biochemical changes related to physiological requirements. CB is “a homeostatic organ,” able to respond to oxygen, carbon dioxide, and blood pH variations (Lahiri et al 1989). These responses induce an increase in chemosensory discharge that arrives to the respiratory centers of the central nervous system, resulting in several effects. CB influences ventilation as well as the sympathetic nervous system responses such as heart rate, hormonal changes, etc. Because CB is a “stress” receptor, evaluation of CB after chronic stimuli could give insight into its structural and functional modifications correlated with the aging processes. These experimental conditions could be of use in establishing whether the carotid body could be used as a model for the study of the aging processes. CB catecholamine (CA) content is increased as a result of oxygen supply variations. For example, during chronic hypoxia (10% PIO2) and chronic hyperoxia (100% PIO2) the CA increase seems to represent the common response to both “stress” situations (Mokashi et al 1994). Although during acute hypoxia CB dopamine release (Buerk et al 1995) is still controversial, nonetheless its release in stress situations is well documented. The aging process is characterized by an increase in CB catecholamine content (Hansen 1989; Donelly and Doyle 1993); this same phenomenon can also be observed in blood during chronic hypoxia (Mazzeo 1993). Several experimental lines suggest a reduction of β-sensitivity during chronic hypoxia (Maher et al 1975; Kacimi et al 1995) and aging (Ford et al 1995); therefore, a correlation between chronic hypoxia and aging cannot be ruled out. Moreover, Cerretelli et al (1991)) found an increase in muscle lipofuscin, a marker of aging, in Sherpa living at high altitudes.
On the other hand, hyperoxia is not a physiological condition, but cells are in many cases exposed to a relative increase in oxygen supply and free radical production due to, for example, the organs flow perfusion (Jamieson 1989; Torbati et al 1993). Paul Bert (Dejours and Dejours 1992) was the first to emphasise that prolonged hyperoxia is not compatible with the survival of aerobic organisms, and Mokashi (Mokashi et al 1994) demonstrated that the carotid chemosensory response to hypoxia was attenuated after chronic normobaric hyperoxia, while hypercapnic response was unaltered. A similar process has also been shown during aging (Miquel et al 1992).
The aim of this study was to compare the effect of hyperoxia in young and old rats CBs and the corresponding age-dependent modifications using chronic hyperoxia, which could represent an experimental model of aging.
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Materials and Methods
Experiments were performed on four groups of Wistar male rats. One group was composed of six young rats (two months), another of six aged rats (25 months), two more groups of six rats (age-matched: 2 and 25 months old) served as controls. The rats belonging to the first two groups were exposed to 98–100% O2 (Normobaric hyperoxia), for 60–65 h, in a large Plexiglas chamber. The chamber air was recirculated by the use of a pump, and CO2 was removed from the chamber air with Baralyme and was
Ultrastructural Studies
The normal structure of a young rat carotid body is shown in Fig. 1, Fig. 2. Fig. 3, Fig. 4 show an increase in collagen fibers, along with presence of lipofuscin in type I cells ; cytoplasm fibrosis with increase in extracellular matrix of aged rats. The young hyperoxic rat CBs showed focal cellular damage of both type I and type II cells (Fig. 5 and Fig. 6). The parenchyma was characterized by a striking increase in cell membrane structures, endoplasmic reticulum, microfilaments and
Discussion
We studied structural correlates of rat carotid body after chronic hyperoxia of young and old rats, and particularly mitochondria, because they seem to be involved with the aging process (Muller-Hocker 1992).
Hyperoxia is known to generate free radical species (Freeman and Crapo 1981; Jamieson 1989; Torbati et al 1993) and the structural and functional damage they produce to plasma and mitochondria membrane (i.e., lipid peroxidation) should be constantly repaired to allow normal cell function.
Acknowledgements
We are grateful to Marcello Piccirilli for his technical assistance and to Dr. Franca Daniele for her help in correcting the manuscript.
References (18)
- et al.
Hyperoxia increases oxygen radical production in rat lung mithochondria
J. Biol. Chem.
(1981) Oxygen toxicity and reactivbe oxygen metabolites in mammals
Free Radic. Biol. Med.
(1989)- et al.
Chronic hyperoxic effects on cat carotid body catecholamines and structure
Respir. Physiol.
(1994) - et al.
Hyperbaric oxygenation alters carotid body ultrastructure and function
Respir. Physiol.
(1993) - et al.
Electrochemical detection of rapid DA release kinetics during hypoxia in perfused-superfused cat CB
J. Appl. Physiol.
(1995) - et al.
Muscle function at altitude
- et al.
The effects of barometric pressure according to Paul BertThe question today
Int. J. Sport Med.
(1992) - et al.
Free tissue catecholamines of rat carotid body, in vitro, during maturation and following chronic hypoxia
Soc. Neurosci. Abstr.
(1993) - et al.
Effect of aging on β2adrenergic receptor-stimulated flux of K+, PO4, FFA, and glycerol in human forearms
J. Appl. Physiol.
(1995)