Strain-associated differences in hypoxic chemosensitivity of the carotid body in rats.

Studies in humans indicate genetic effects on the ventilatory response to hypoxia, but the site of these effects is unknown. The present study explores the question of whether there are genetically directed effects on the intrinsic hypoxic chemosensitivity of the carotid body. The approach was to study these responses in two inbred rat strains [spontaneously hypertensive rats (SHR) and Fischer 344 (F-344)] and to measure in vivo carotid chemosensitivity as the change in carotid sinus nerve (CSN) activity during progressive, isocapnic hypoxia and the isolated, in vitro responses of excised superfused carotid bodies, loaded with the fluorimetric indicator fura 2, measured as the cytosolic calcium response to moderate hypoxia (PO2 = 55 mmHg). CSN responses in F-344 rats (n = 12) were uniformly low, with a shape parameter A of 13.8 +/- 6.59 (SE), whereas responses in SHR (n = 15) were sevenfold higher (108 +/- 24.1; P < 0.002) and showed greater variation. In vitro, intracellular calcium responses of superfused carotid bodies estimated from the fluorimetric ratio (340/380 nm) showed a greater peak increase during hypoxia in carotid bodies from SHR (140 +/- 4.7%) than from F-344 rats (114 6.0%; P < 0.01). Our results indicate strain-related differences in hypoxic chemosensitivity that are intrinsic to the carotid body and that could mediate genetic effects on ventilatory responsiveness to hypoxia.

[1]  N. Anthonisen,et al.  Familial aspects of ventilatory control in patients with chronic obstructive pulmonary disease. , 2015, The American review of respiratory disease.

[2]  Y. Kawakami,et al.  Familial factors affecting arterial blood gas values and respiratory chemosensitivity in chronic obstructive pulmonary disease. , 2015, The American review of respiratory disease.

[3]  W. Mitzner,et al.  Genetic control of differential baseline breathing pattern. , 1997, Journal of applied physiology.

[4]  S. Kleeberger,et al.  Modified control of breathing in genetically obese (ob/ob) mice. , 1996, Journal of applied physiology.

[5]  F. Agani,et al.  Heterogeneity in cytosolic calcium responses to hypoxia in carotid body cells , 1996, Brain Research.

[6]  S. Kleeberger,et al.  Differential control of ventilation among inbred strains of mice. , 1994, The American journal of physiology.

[7]  Y Kikuchi,et al.  Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma. , 1994, The New England journal of medicine.

[8]  J. Severinghaus,et al.  Augmented hypoxic ventilatory response in men at altitude. , 1992, Journal of applied physiology.

[9]  A. Trzebski.  Arterial chemoreceptor reflex and hypertension. , 1992, Hypertension.

[10]  D. Donnelly,et al.  Hypoxia decreases intracellular calcium in adult rat carotid body glomus cells. , 1992, Journal of neurophysiology.

[11]  A. Dominiczak,et al.  The primacy of membrane microviscosity in genetic hypertension. , 1991, American journal of hypertension.

[12]  M. Shirahata,et al.  Dependency of hypoxic chemotransduction in cat carotid body on voltage-gated calcium channels. , 1991, Journal of applied physiology.

[13]  J. Habeck.  Peripheral arterial chemoreceptors and hypertension. , 1991, Journal of the autonomic nervous system.

[14]  N. Voelkel,et al.  Pulmonary vascular reactivity in Fischer rats. , 1991, Journal of applied physiology.

[15]  S. Lahiri,et al.  In vitro perfused-superfused cat carotid body for physiological and pharmacological studies. , 1991, Journal of applied physiology.

[16]  J. Weil,et al.  Attenuated carotid body hypoxic sensitivity after prolonged hypoxic exposure. , 1991, Journal of applied physiology.

[17]  L. Moore,et al.  Decreased ventilation and hypoxic ventilatory responsiveness are not reversed by naloxone in Lhasa residents with chronic mountain sickness. , 1990, The American review of respiratory disease.

[18]  A. Dominiczak,et al.  Cell membrane abnormalities and the regulation of intracellular calcium concentration in hypertension. , 1990, Clinical science.

[19]  M. Duchen,et al.  Cellular basis of transduction in carotid chemoreceptors. , 1990, The American journal of physiology.

[20]  A. Tucker,et al.  Sympathetic and Metabolic Correlates of Hypoxic Moderation of Spontaneous Hypertension in the Rat , 1989, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[21]  F. Abboud,et al.  Potentiation of Sympathetic Nerve Responses to Hypoxia in Borderline Hypertensive Subjects , 1988, Hypertension.

[22]  W. Mills,et al.  Abnormal control of ventilation in high-altitude pulmonary edema. , 1988, Journal of applied physiology.

[23]  J. Weil,et al.  Increased carotid body hypoxic sensitivity during acclimatization to hypobaric hypoxia. , 1987, Journal of applied physiology.

[24]  J. Weil,et al.  Interindividual variation in hypoxic ventilatory response: potential role of carotid body. , 1987, Journal of applied physiology.

[25]  R. Schoene,et al.  Control of ventilation in elite synchronized swimmers. , 1987, Journal of applied physiology.

[26]  D. White,et al.  Altitude acclimatization: influence on periodic breathing and chemoresponsiveness during sleep. , 1987, Journal of applied physiology.

[27]  Y. Fukuda,et al.  Carotid chemoreceptor discharge responses to hypoxia and hypercapnia in normotensive and spontaneously hypertensive rats. , 1987, Journal of the autonomic nervous system.

[28]  Y. Yazaki,et al.  The elevation of the cytoplasmic calcium ions in vascular smooth muscle cells in SHR--measurement of the free calcium ions in single living cells by lasermicrofluorospectrometry. , 1986, Biochemical and biophysical research communications.

[29]  L. Moore,et al.  Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness. , 1986, Journal of applied physiology.

[30]  R. Schoene.  Control of ventilation in climbers to extreme altitude. , 1982, Journal of applied physiology: respiratory, environmental and exercise physiology.

[31]  Y. Kawakami,et al.  Control of breathing in young twins. , 1982, Journal of applied physiology: respiratory, environmental and exercise physiology.

[32]  A. Trzebski,et al.  Increased sensitivity of the arterial chemoreceptor drive in young men with mild hypertension. , 1982, Cardiovascular research.

[33]  J. Feingold,et al.  Inheritance of abnormal erythrocyte cation transport in essential hypertension. , 1981, British medical journal.

[34]  P. Hackett,et al.  Control of breathing in Sherpas at low and high altitude. , 1980, Journal of applied physiology: respiratory, environmental and exercise physiology.

[35]  J. Weil,et al.  Hereditary aspects of decreased hypoxic response. , 1978, The Journal of clinical investigation.

[36]  J. Weil,et al.  Hypoventilation in obstructive lung disease. The role of familial factors. , 1978, The New England journal of medicine.

[37]  J. Weil,et al.  Familial aspects of decreased hypoxic drive in endurance athletes. , 1978, Journal of applied physiology: respiratory, environmental and exercise physiology.

[38]  J. Weil,et al.  Effects of hypermetabolism on ventilation and chemosensitivity. , 1977, The Journal of clinical investigation.

[39]  A. Krieger,et al.  Carotid and aortic chemoreceptor function in the rat. , 1977, Journal of applied physiology: respiratory, environmental and exercise physiology.

[40]  J. Weil,et al.  Respiratory failure associated with familial depression of ventilatory response to hypoxia and hypercapnia. , 1976, The New England journal of medicine.

[41]  S. Leeder,et al.  Ventilatory response to carbon dioxide in young athletes: a family study. , 1976, The American review of respiratory disease.

[42]  S. Lakshminarayan,et al.  Recurrent high altitude pulmonary edema with blunted chemosensitivity. , 1975, The American review of respiratory disease.

[43]  C. Hirshman,et al.  Normal values for hypoxic and hypercapnic ventilaroty drives in man. , 1975, Journal of applied physiology.

[44]  D. Hudgel,et al.  Asthma associated with decreased hypoxic ventilatory drive. A family study. , 1974, Annals of internal medicine.

[45]  J. Weil,et al.  A new approach to quantitation of whole nerve bundle activity. , 1974, Journal of applied physiology.

[46]  F. Fay.  Oxygen consumption of the carotid body. , 1970, The American journal of physiology.

[47]  J. W. Spickler,et al.  Probability of spike summations in baroreceptor electroneurograms. , 1969, Journal of applied physiology.

[48]  J. Weil,et al.  A modified fuel cell for the analysis of oxygen concentration of gases. , 1967, Journal of applied physiology.

[49]  J. García-Sancho,et al.  Ca2+ dynamics in chemoreceptor cells: an overview. , 1993, Advances in experimental medicine and biology.

[50]  R. Stoohs,et al.  Attenuation of augmented ventilatory response to hypoxia in essential hypertension in the course of aging. , 1989, Respiration; international review of thoracic diseases.

[51]  J. Habeck,et al.  The carotid bodies of hypertensive/normotensive hybrid rats. , 1987, Biomedica biochimica acta.

[52]  G. Barer,et al.  Size of the carotid body and ventilatory responses to hypoxia in genetically hypertensive rats. , 1987, Biomedica biochimica acta.

[53]  A. Trzebski,et al.  Augmented chemoreceptor reflex tonic drive in early human hypertension and in normotensive subjects with family background of hypertension. , 1985, Acta physiologica Polonica.

[54]  H. Holzhausen,et al.  An ultrastructural study of the vascular alterations within the carotid bodies of spontaneously hypertensive rats (SHR). , 1985, Experimental pathology.

[55]  I. McMurtry,et al.  Pulmonary vascular reactivity in the spontaneously hypertensive rat. , 1979, Blood vessels.

[56]  R. O'Regan.  Responses of the chemoreceptors of the cat carotid body perfused with cell-free solutions , 1979, Irish journal of medical science.

[57]  J. Weil,et al.  Ventilatory control in the athlete. , 1971, Journal of applied physiology.

[58]  J. Weil,et al.  Acquired attenuation of chemoreceptor function in chronically hypoxic man at high altitude. , 1971, The Journal of clinical investigation.