Influence of acute progressive hypoxia on cardiovascular variability in conscious spontaneously hypertensive rats

The purpose of this study is to examine the influence of acute progressive hypoxia on cardiovascular variability and striatal dopamine (DA) levels in conscious, spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). After preparation for measurement, the inspired oxygen concentration of rats was decreased to 10% within 5 min (descent stage), maintained at 10% for 10 min (fixed stage), and then elevated back to 20% over 5 min (recovery stage). The systolic blood pressure (SBP) and heart rate (HR) variability at each stage was calculated to evaluate the autonomic nervous system response using the wavelet method. Striatal DA during each stage was measured using in vivo microdialysis. We found that SHR showed a more profound hemodynamic response to progressive hypoxia as compared to WKY. Cardiac parasympathetic activity in SHR was significantly inhibited by acute progressive hypoxia during all stages, as shown by the decrease in the high frequency band of HR variability (HR-HF), along with transient increase in sympathetic activity during the early hypoxic phase. This decrease in the HR-HF continued even when SBP was elevated. Striatal DA levels showed the transient similar elevation in both groups. These findings suggest that acute progressive hypoxic stress in SHR inhibits cardiac parasympathetic activity through reduction of baroreceptor reflex sensitivity, with potentially severe deleterious effects on circulation, in particular on HR and circulatory control. Furthermore, it is thought that the influence of acute progressive hypoxia on striatal DA levels is similar in SHR and WKY.

[1]  D R Brown,et al.  Sympathetic activity and blood pressure are tightly coupled at 0.4 Hz in conscious rats. , 1994, The American journal of physiology.

[2]  N. Terui,et al.  Differential responsiveness of RVLM sympathetic premotor neurons to hypoxia in rabbits. , 2007, American journal of physiology. Heart and circulatory physiology.

[3]  J. Hayano,et al.  Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. , 1991, The American journal of cardiology.

[4]  R. Cohen,et al.  Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. , 1981, Science.

[5]  L. Denoroy,et al.  Dopamine transporters are involved in the onset of hypoxia-induced dopamine efflux in striatum as revealed by in vivo microdialysis , 2005, Neurochemistry International.

[6]  T. Hedner,et al.  Regional changes in monoamine synthesis in the developing rat brain during hypoxia. , 1979, Acta physiologica Scandinavica.

[7]  Stephan Zipfel,et al.  Autonomic Neuroscience: Basic and Clinical , 2010 .

[8]  M. Turiel,et al.  Power Spectral Analysis of Heart Rate and Arterial Pressure Variabilities as a Marker of Sympatho‐Vagal Interaction in Man and Conscious Dog , 1986, Circulation research.

[9]  J. Belmin,et al.  Arterial Stiffness Is Associated with Orthostatic Hypotension in Elderly Subjects with History of Falls , 2004, Journal of the American Geriatrics Society.

[10]  Metin Akay,et al.  Introduction: Wavelet transforms in biomedical engineering , 1995, Annals of Biomedical Engineering.

[11]  Shlomo Havlin,et al.  Scaling behaviour of heartbeat intervals obtained by wavelet-based time-series analysis , 1996, Nature.

[12]  C Cerutti,et al.  Autonomic nervous system and cardiovascular variability in rats: a spectral analysis approach. , 1991, The American journal of physiology.

[13]  V Pichot,et al.  Wavelet transform to quantify heart rate variability and to assess its instantaneous changes. , 1999, Journal of applied physiology.

[14]  J. Marshall,et al.  A link between adenosine, ATP‐sensitive K+ channels, potassium and muscle vasodilatation in the rat in systemic hypoxia. , 1993, The Journal of physiology.

[15]  B. Walker,et al.  Contribution of oxygen radicals to altered NO-dependent pulmonary vasodilation in acute and chronic hypoxia. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[16]  Y. Fukuda,et al.  Autonomic nerve and cardiovascular responses to changing blood oxygen and carbon dioxide levels in the rat. , 1989, Journal of the autonomic nervous system.

[17]  G. Head CARDIAC BAROREFLEXES AND HYPERTENSION , 1994, Clinical and experimental pharmacology & physiology.

[18]  M. Geffard,et al.  Central dopamine-synthesis regulation by the calcium-calmodulin-dependent system , 1989, Brain Research Bulletin.

[19]  R. Busto,et al.  Effect of Ischemia on the In Vivo Release of Striatal Dopamine, Glutamate, and γ‐Aminobutyric Acid Studied by Intracerebral Microdialysis , 1988, Journal of neurochemistry.

[20]  U. Tuor,et al.  Long-Term Deficits Following Cerebral Hypoxia–Ischemia in Four-Week-Old Rats: Correspondence between Behavioral, Histological, and Magnetic Resonance Imaging Assessments , 2001, Experimental Neurology.

[21]  Y. Hayashida,et al.  Effect of carbon dioxide on autonomic cardiovascular responses to systemic hypoxia in conscious rats. , 1997, The American journal of physiology.

[22]  J. Hayano,et al.  Effects of respiratory interval on vagal modulation of heart rate. , 1994, The American journal of physiology.

[23]  J. Marshall,et al.  The role of adenosine in mediating vasodilatation in mesenteric circulation of the rat in acute and chronic hypoxia. , 1995, The Journal of physiology.

[24]  A. Otsuka,et al.  Spectral change in heart rate variability in response to mental arithmetic before and after the beta-adrenoceptor blocker, carteolol , 2005, Clinical Autonomic Research.

[25]  G. Hagberg,et al.  MILD MENTAL RETARDATION IN SWEDISH SCHOOL CHILDREN , 1981, Acta paediatrica Scandinavica.

[26]  S. Ancoli-Israel,et al.  The effect of hypoxia on baroreflexes and pressor sensitivity in sleep apnea and hypertension. , 1995, Sleep.

[27]  D. Sutoo,et al.  Decrease of central dopamine level in the adult spontaneously hypertensive rats related to the calcium metabolism disorder , 1993, Brain Research Bulletin.

[28]  S. Morrison,et al.  Disinhibition of rostral raphe pallidus neurons increases cardiac sympathetic nerve activity and heart rate , 2003, Brain Research.

[29]  B. Siesjö,et al.  The density and distribution of ischemic brain injury in the rat following 2–10 min of forebrain ischemia , 2004, Acta Neuropathologica.

[30]  L. Tavazzi,et al.  Depressed arterial baroreflex sensitivity and not reduced heart rate variability identifies patients with chronic heart failure and nonsustained ventricular tachycardia: the effect of high ventricular filling pressure. , 1997, American Heart Journal.

[31]  S Cerutti,et al.  Sympathetic predominance in essential hypertension: a study employing spectral analysis of heart rate variability. , 1988, Journal of hypertension.

[32]  S. Morrison,et al.  Medullary pathways mediating specific sympathetic responses to activation of dorsomedial hypothalamus , 2004, Neuroscience.

[33]  Y. Tomita,et al.  Role of Vagal Control in Vasovagal Syncope , 2003, Pacing and clinical electrophysiology : PACE.

[34]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[35]  G Stockmanns,et al.  Wavelet Analysis of Middle Latency Auditory Evoked Responses: Calculation of an Index for Detection of Awareness during Propofol Administration , 2001, Anesthesiology.

[36]  M. N. Levy,et al.  Autonomic control of cardiac pacemaker activity and atrioventricular transmission. , 1969, Journal of applied physiology.

[37]  D. Adam,et al.  Assessment of autonomic function in humans by heart rate spectral analysis. , 1985, The American journal of physiology.

[38]  P. Friberg,et al.  Sympathetic and parasympathetic influence on blood pressure and heart rate variability in Wistar—Kyoto and spontaneously hypertensive rats , 1988, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[39]  Yoshinobu Murasato,et al.  Effects of systemic hypoxia on R-R interval and blood pressure variabilities in conscious rats. , 1998, American journal of physiology. Heart and circulatory physiology.

[40]  K. Hecht,et al.  The vulnerable period of perinatal hypoxia with regard to dopamine release and behaviour in adult rats. , 1986, Biomedica biochimica acta.

[41]  K. Shimada,et al.  Age-related changes of baroreflex function, plasma norepinephrine, and blood pressure. , 1985, Hypertension.

[42]  R. Busto,et al.  Cerebal norepinephrine depletion enhances recovery after brain ischemia , 1985, Annals of neurology.

[43]  J. Elghozi,et al.  Effects of graded hemorrhage on short‐term variability of blood pressure in conscious rats , 1996, Fundamental & clinical pharmacology.

[44]  T. Ogihara,et al.  Changes in autonomic activity and baroreflex sensitivity with the hypertension process and age in rats , 2003, Clinical and experimental pharmacology & physiology.

[45]  A. Ishida,et al.  Effect of anoxia on striatal monoamine metabolism in immature rat brain compared with that of hypoxia: an in vivo microdialysis study , 1996, Brain Research.

[46]  G. Haddad,et al.  Mechanisms underlying hypoxia-induced neuronal apoptosis , 2000, Progress in Neurobiology.

[47]  G. Hagberg,et al.  MILD MENTAL RETARDATION IN SWEDISH SCHOOL CHILDREN , 1981, Acta paediatrica Scandinavica.

[48]  D. Laude,et al.  Spectral analysis of blood pressure and heart rate in conscious rats: effects of autonomic blockers. , 1990, Journal of the autonomic nervous system.

[49]  P. Friberg,et al.  Increased myocardial repolarization lability and reduced cardiac baroreflex sensitivity in individuals with high-normal blood pressure , 2005, Journal of hypertension.

[50]  L. Seiden,et al.  Age-dependent effects of 6-hydroxydopamine on locomotor activity in the rat , 1979, Brain Research.

[51]  D. Reis,et al.  Hypoxia selectively excites vasomotor neurons of rostral ventrolateral medulla in rats. , 1994, The American journal of physiology.

[52]  T. Kawaguchi,et al.  Cardiovascular and autonomic nervous functions during acclimatization to hypoxia in conscious rats , 2005, Autonomic Neuroscience.

[53]  D. Sutoo,et al.  Neurochemical changes in mice following physical or psychological stress exposures , 2002, Behavioural Brain Research.

[54]  P. Friberg,et al.  Autonomic control of the diurnal variation in arterial blood pressure and heart rate in spontaneously hypertensive and Wistar-Kyoto rats. , 1989, Journal of Hypertension.

[55]  J. Marshall,et al.  Analysis of the cardiovascular changes induced in the rat by graded levels of systemic hypoxia. , 1988, The Journal of physiology.

[56]  Yoshio Furukawa,et al.  Wavelet transform analysis of heart rate variability to assess the autonomic changes associated with spontaneous coronary spasm of variant angina. , 2003, Journal of electrocardiology.

[57]  J. Neubauer,et al.  Oxygen-sensing neurons in the central nervous system. , 2004, Journal of applied physiology.