Modulation of sympathetic vasoconstriction is critical for the effects of sleep on arterial pressure in mice

Abstract

The values of arterial pressure (AP) during sleep predict cardiovascular risk. Sleep exerts similar effects on cardiovascular control in human subjects and mice. We aimed to determine the underlying autonomic mechanisms in 12 C57Bl/6J mice with a novel technique of intraperitoneal infusion of autonomic blockers, while monitoring the electroencephalogram, electromyogram, AP and heart period (HP, i.e. 1/heart rate). In different sessions, we administered atropine methyl nitrate, atenolol and prazosin to block muscarinic cholinergic, β -adrenergic and α -adrenergic receptors, respectively, and compared each drug infusion with a matched vehicle infusion. The decrease in AP from wakefulness to non-rapid-eye-movement sleep (N) was abolished by prazosin but was not significantly affected by atropine and atenolol, which, however, blunted the accompanying increase in HP to a similar extent. On passing from N to rapid-eye-movement sleep (R), the increase in AP was significantly blunted by prazosin and atenolol, whereas the accompanying decrease in HP was blunted by atropine and abolished by atenolol. Cardiac baroreflex sensitivity (cBRS, sequence technique) was dramatically decreased by atropine and slightly increased by prazosin. These data indicate that in C57Bl/6J mice, N decreases mean AP by decreasing sympathetic vasoconstriction, increases HP by balancing parasympathetic activation and sympathetic withdrawal, and increases cBRS mainly by increasing fluctuations in parasympathetic activity. R increases mean AP by increasing sympathetic vasoconstriction and cardiac sympathetic activity, which also explains, at least in part, the concomitant decrease in HP. These data represent the first comprehensive assessment of the autonomic mechanisms of cardiovascular control during sleep in mice.

Dynamic coupling between the central and autonomic nervous systems during sleep: A review

“…Neurons of the nucleus of the solitary tract control both cardiac parasympathetic activity, by means of a direct projection to preganglionic parasympathetic neurons in the nucleus ambiguus of the medulla, and cardiac SNA, by means of indirect projections to the rostral ventrolateral medulla (Silvani et al, 2016). At least in mice, the decrease in heart rate from wakefulness to NREM sleep is caused by strikingly balanced increases and decreases in parasympathetic and sympathetic tone to the heart, respectively (Lo Martire et al, IN PRESS). Sleep-related changes in the neural circuit involving the parabrachial nucleus and the nucleus of the solitary tract may thus contribute to drive the decrease in heart rate during NREM sleep.…”

“…The tonic periods of REM sleep entail disparate changes in SNA, consisting of decreases in renal and mesenteric SNA and simultaneous increases in skeletal muscle SNA (Yoshimoto et al, 2011). Moreover, recent data on mice indicate that the increase in heart rate on passing from NREM sleep to REM sleep is mediated, at least in part, by an increase in cardiac SNA (Lo Martire et al, IN PRESS). The increases in muscle and cardiac SNA during REM sleep may result from direct excitatory projections from the pontine sublaterodorsal nucleus to the pre-sympathetic neurons in the rostral medulla, which project to the sympathetic preganglionic neurons.…”

Is Adenosine Action Common Ground for NREM Sleep, Torpor, and Other Hypometabolic States?

“…The fall in metabolic rate during NREM sleep is accompanied by a decrease in heart rate and arterial pressure, both in human subjects and in small model animals (145). This decrease in arterial pressure may result from the decrease in heart rate, itself due to a balance of cardiac sympathetic withdrawal and parasympathetic activation (87), in the absence of a compensatory increase in stroke volume and/or peripheral resistance (74). Indeed, recent evidence indicates that, at least in mice, the decrease in arterial pressure during NREM sleep depends critically from a reduction in sympathetic vasoconstriction (87), possibly due to a reduction in sympathetic activity to the vasculature of skeletal muscles (147), kidneys (177), and skin (163).…”

“…This decrease in arterial pressure may result from the decrease in heart rate, itself due to a balance of cardiac sympathetic withdrawal and parasympathetic activation (87), in the absence of a compensatory increase in stroke volume and/or peripheral resistance (74). Indeed, recent evidence indicates that, at least in mice, the decrease in arterial pressure during NREM sleep depends critically from a reduction in sympathetic vasoconstriction (87), possibly due to a reduction in sympathetic activity to the vasculature of skeletal muscles (147), kidneys (177), and skin (163). However, since both arterial pressure and regional vascular resistance may decrease during NREM sleep, peripheral blood flow to non-skin organs may not change greatly during NREM sleep (26,82,93,115).…”

Functions of sensory TRP channels in vascular responses to chemical and thermal stimuli

“…In resistance arteries, sympathetic vasoconstrictor fibres are tonically active releasing NA that binds mainly to a 1 -adrenergic receptors located in the VSMC, resulting in a constriction of the blood vessels [10]. This means that a reduced sympathetic vasomotor activity causes vasodilatation [7].…”