Chemoreceptors and cardiovascular control in acute and chronic systemic hypoxia

Abstract

This review describes the ways in which the primary bradycardia and peripheral vasoconstriction evoked by selective stimulation of peripheral chemoreceptors can be modified by the secondary effects of a chemoreceptor-induced increase in ventilation. The evidence that strong stimulation of peripheral chemoreceptors can evoke the behavioural and cardiovascular components of the alerting or defence response which is characteristically evoked by novel or noxious stimuli is considered. The functional significance of all these influences in systemic hypoxia is then discussed with emphasis on the fact that these reflex changes can be overcome by the local effects of hypoxia: central neural hypoxia depresses ventilation, hypoxia acting on the heart causes bradycardia and local hypoxia of skeletal muscle and brain induces vasodilatation. Further, it is proposed that these local influences can become interdependent, so generating a positive feedback loop that may explain sudden infant death syndrome (SIDS). It is also argued that a major contributor to these local influences is adenosine. The role of adenosine in determining the distribution of O 2 in skeletal muscle microcirculation in hypoxia is discussed, together with its possible cellular mechanisms of action. Finally, evidence is presented that in chronic systemic hypoxia, the reflex vasoconstrictor influences of the sympathetic nervous system are reduced and/or the local dilator influences of hypoxia are enhanced. In vitro and in vivo findings suggest this is partly explained by upregulation of nitric oxide (NO) synthesis by the vascular endothelium which facilitates vasodilatation induced by adenosine and other NO-dependent dilators and attenuates noradrenaline-evoked vasoconstriction. Correspondence

Effect of acute systemic hypoxia on human cutaneous microcirculation and endothelial, sympathetic and myogenic activity

“…Other explanation of skin blood flows increase could be due to systemic hemodynamic changes (Table 4) which could be caused by sympatho-vagal tonus impact to heart (Table 2). It is known that acute systemic hypoxia, either direct or as a result of reflex hyperventilation, stimulates the chemoreceptors, which in turn activate the sympatho-adrenergic axis (Marshall 1998, Povea et al 2005 in such kind of way acute hypoxic exposure affects cardiovascular autonomic functions (Huang et al 2009). During exposure to hypoxic environments, such us high altitudes or artificial hypoxia, RR variability in heart rate is reduced with a relative increase in the low-frequency component, indicating changed cardiac autonomic activity of the sinus node in response to hypoxic stimulation (Huang et al 2009).…”

Role of posterior hypothalamus in hypobaric hypoxia induced pulmonary edema

“…Stimulation of peripheral chemoreceptors by hypoxia could result in an increased respiratory drive, an increase in heart rate and vasoconstriction. Increased ventilation could lead to stimulation of lung stretch receptors, hypocapnia, increase heart rate and cause vasodilation especially in skeletal muscles (Marshal, 1998). Additional contributions could come from the hypothalamic defence area stimulation of which also increase heart rate, cause vasoconstriction in splanchnic and renal bed and vasodilatation in skeletal muscle (Abrahams et al, 1960).…”

“…In the next 20 min, these responses were less marked. Hypoxia could depress myocardial activity, cause bradycardia and promote vasodilatation by its direct effect on the tissues of the systemic circulation (Marshal, 1998). Thus, the final effect of hypoxia on the cardiovascular system would depend upon the balance among these factors.…”

Transient peripheral warming accompanies the hypoxic metabolic response in the golden-mantled ground squirrel

“…Local effects can result from the oxygen-limited metabolism of the smooth muscle of arterioles, through the release of metabolically derived vasodilatory substances. Central effects are integrated in the hypothalamus, and are mediated through the sympathetic nervous system acting on the blood vessels themselves, effecting either vasodilation or vasoconstriction (Klir and Heath, 1994;Marshall, 1998). Cutaneous blood flow, and thus Ts and heat loss, are mainly under central sympathetic nervous control (Jänig, 1990), while local factors play a small role under normal conditions.…”