Role of purinergic cotransmission in the sympathetic control of arterial pressure variability in conscious rats

Abstract

Previous studies have shown that the sympathetically mediated oscillations of arterial pressure (AP), the so-called Mayer waves, are shifted from 0.4 to 0.6 Hz after acute alpha-adrenoceptor blockade in conscious rats. This raises the possibility that, under physiological conditions, Mayer waves are mediated by the conjoint action of norepinephrine and other sympathetic cotransmitters. To evaluate the possible role of the cotransmitter ATP in determining the frequency of Mayer waves, AP and renal sympathetic nerve activity (RSNA) were simultaneously recorded in 10 conscious rats with cardiac autonomic blockade before and after acute blockade of P2 receptors with pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid. P2 receptor blockade did not alter the mean level and overall variability of AP and RSNA but shifted peak coherence between AP and RSNA from 0.43 +/- 0.02 to 0.22 +/- 0.01 Hz. A model of the sympathetic limb of the arterial baroreceptor reflex was designed to simulate Mayer waves at 0.2 and 0.6 Hz, with norepinephrine and ATP, respectively, acting as the sole sympathetic cotransmitter. When both cotransmitters acted in concert, a single oscillation was observed at 0.4 Hz when the gain ratio of the adrenergic to the purinergic components was set at 15. The model thus accounted for an important role for ATP in determining Mayer wave frequency, but not in sustaining the mean level of AP or controlling its overall variability.

An update on the enigma of Mayer waves

“…6 In 2006, I briefly mentioned the possible role of the cotransmitter of noradrenaline, ATP, in the determinism of the central frequency of Mayer waves. Very shortly after, 7 we had confirmation in conscious rats that the maximum coherence between BP and renal SNA was shifted from 0.4 to 0.2 Hz after P2 receptor blockade, thus confirming that ATP plays an important role in determining the frequency of Mayer waves. Whether ATP is important in between-species differences in Mayer wave frequency remains to be investigated.…”

General Principles of Neuronal Co-transmission: Insights From Multiple Model Systems

“…ATP has been subsequently found to co-localize with various transmitters in the peripheral and CNS (see Table 1 and reviews by Westfall et al, 1978; Burnstock, 2007; Wier et al, 2009; Hill-Eubanks et al, 2010; Hnasko and Edwards, 2012; Kennedy, 2015). For example, purinergic co-transmission is involved in the sympathetic control of arterial pressure in rats (Emonnot et al, 2006); as a co-transmitter with ACh in carotid body arterial chemoreceptors (Zapata, 2007); in the human carotid body where ACh, ATP and cytokines are co-released during hypoxia (Kåhlin et al, 2014); ATP and glutamate are released ectopically from vesicles along axons to mediate neurovascular coupling via glial calcium signaling (Thyssen et al, 2010); co-localized ATP and NA are involved in the sympathetic thermoregulatory response to cooling (Kozyreva et al, 2015); and ATP is released from dopaminergic neurons of the mouse retina and midbrain (Ho et al, 2015). For reviews describing the physiological significance of purinergic co-transmission see Burnstock (2004, 2014).…”

Dysregulation of Norepinephrine Release in the Absence of Functional Synaptotagmin 7

“…Many proteins and hormones are involved in regulating the expression levels of NET in the plasma membrane, which are directly correlated with the function of NET [Sager and Torres, ]. In noradrenergic neurons, NE‐containing vesicles also contain other transmitters and hormones in addition to NE [Hammond et al, ; Emonnot et al, ; Li et al, ]. Therefore, it is also possible that one of these co‐transmitters, which cannot be released by the Syt7‐regulated exocytosis, is required to downregulate the expression levels of NET in the plasma membrane of cardiac sympathetic nerve terminals.…”