Regulation of arterial oxygen levels is critically important in mammals, particularly during early life. Peri-and postnatal hypoxia may lead to impaired cognitive development, abnormalities in cardiovascular function, breathing control maturation and lung function, and death (Okubo & Mortola, 1988;Nyakas et al. 1996;Hudlicka & Brown, 1996). The main sensors of arterial Oµ tension are the carotid body chemoreceptors, which are located bilaterally at the bifurcations of the common carotid arteries. Carotid chemoreceptor sensory afferents, via the carotid sinus nerves (CSN), project to the nucleus tractus solitarii and other brainstem nuclei, providing the major source of Oµ-mediated ventilatory drive. Neural signals from the carotid chemoreceptors to brainstem cardiorespiratory control nuclei also mediate critically important respiratory reflexes such as arousal from sleep during hypoxia and cardiovascular reflexes that modulate heart rate and blood pressure (Marshall, 1987). The primary site of oxygen sensing in the carotid body is thought to be the type I cell (Gonzalez et al. 1994). Type I cells are specialized sensory neurons which depolarize in response to low Oµ, resulting in Ca¥ entry via voltage-gated calcium channels, and exocytosis of neurotransmitters and modulators onto apposed CSN terminals (Gonzalez et al. 1994). Although further study is needed to define their precise role, there is little question that type I cells play a crucial role in carotid chemoreceptor oxygen sensing. Carotid denervation, which is well tolerated by adults, in neonates leads to profound abnormalities of respiratory control and high mortality rates. In piglets and in lambs the
The site of postnatal maturation of carotid body chemoreception is unclear. To test the hypothesis that maturation occurs synchronously in type I cells and the whole carotid body, the development of changes in the intracellular Ca2+ concentration responses to hypoxia, CO2, and combined challenges was studied with fluorescence microscopy in type I cells and compared with the development of carotid sinus nerve (CSN) responses recorded in vitro from term fetal to 3-wk animals. Type I cell responses to all challenges increased between 1 and 8 days and then remained constant, with no multiplicative O2-CO2interaction at any age. The CSN response to hypoxia also matured by 8 days, but CSN responses to CO2 did not change significantly with age. Multiplicative O2-CO2interaction occurred in the CSN response at 2–3 wk but not in younger groups. We conclude that type I cell maturation underlies maturation of the CSN response to hypoxia. However, because development of responses to CO2 and combined hypoxia-CO2 challenges differed between type I cells and the CSN, responses to these stimuli must mature at other, unidentified sites within the developing carotid body.
The O2 sensitivity of carotid chemoreceptor type I cells is low just after birth and increases with postnatal age. Chronic hypoxia during postnatal maturation blunts ventilatory and carotid chemoreceptor neural responses to hypoxia, but the mechanism remains unknown. We tested the hypothesis that chronic hypoxia from birth impairs the postnatal increase in type I cell O2 sensitivity by comparing intracellular Ca2+ concentration ([Ca2+]i) responses to graded hypoxia in type I cell clusters from rats born and reared in room air or 12% O2. [Ca2+]ilevels at 0, 1, 5, and 21% O2, as well as with 40 mM K+, were measured at 3, 11, and 18 days of age with use of fura 2 in freshly isolated cells. The [Ca2+]iresponse to elevated CO2/low pH was measured at 11 days. Chronic hypoxia from birth abolished the normal developmental increase in the type I cell [Ca2+]iresponse to hypoxia. Effects of chronic hypoxia on development of [Ca2+]iresponses to elevated K+ were small, and [Ca2+]iresponses to CO2 remained unaffected. Impairment of type I cell maturation was partially reversible on return to normoxic conditions. These results indicate that chronic hypoxia severely impairs the postnatal development of carotid chemoreceptor O2sensitivity at the cellular level and leaves responses to other stimuli largely intact.
Upper airway collapsibility may be influenced by both muscular and nonmuscular factors. Because mucosal blood volume (and therefore vascular tone) is an important determinant of nasal airway patency, vascular tone may be an important nonmuscular determinant of pharyngeal collapsibility. This hypothesis was tested in two experimental models. First, upper airway closing (CP) and opening (OP) pressures and static compliance were measured in nine anesthetized, sinoaortic-denervated, paralyzed cats with isolated upper airways. Vascular tone was decreased with either papaverine or sodium nitroprusside (NTP), and increased with phenylephrine (PE), whereas blood pressure and end-tidal CO2 were maintained constant. Vasodilation increased CP (control = -10.4 +/- 1.3, NTP = -7.3 +/- 1.2 cm H2O; p less than 0.05) and OP (control = -7.9 +/- 1.5, NTP = -3.3 +/- 1.8 cm H2O; p less than 0.05). In contrast, vasoconstriction tended to decrease CP (control = -10.7 +/- 1.5, PE = -11.7 +/- 1.4 cm H2O; p less than 0.09) and OP (control = -8.1 +/- 1.2, PE = -9.9 +/- 1.9 cm H2O; p less than 0.1). Thus, vasodilation increased and vasoconstriction tended to decrease upper airway collapsibility. Upper airway static compliance was unchanged during either drug infusion. In order to assess changes in pharyngeal cross-sectional area (CSA) that occurred during vasodilation, magnetic resonance imaging was utilized in seven cats. During vasodilation with NTP, pharyngeal CSA was reduced from 0.44 +/- 0.10 to 0.30 +/- 0.09 cm2 (p less than 0.05), and pharyngeal volume was reduced from 15.3 +/- 2.4 to 13.9 +/- 2.7 cm3 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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