Vagal Involvement in the Action of Exogenous Adenosine Triphosphate on Reflex Renal Sympathetic Nerve Activity

Abstract

The reason why adenine compounds when used as hypotensive agents are devoid of significant reflex sympathetic activity, such as rebound hypertension and tachycardia, is not clearly understood. This study, performed on alpha-chloralose-anesthetized dogs, examined, first, the effects of adenosine triphosphate (ATP) and adenosine as compared with those of sodium nitroprusside on efferent renal sympathetic nerve activity (RSNA), as an indicator of general reflex sympathetic activity, and second, whether vagal involvement could be demonstrated in the action of ATP and adenosine on RSNA. Renal sympathetic nerve activity increased progressively with increasing doses of sodium nitroprusside (5, 10, and 20 micrograms/kg) and adenosine (0.5, 2.0, and 4.0 mg/kg), whereas ATP suppressed RSNA at 2.0 and 4.0 mg/kg. High doses of ATP and adenosine (4.0 mg/kg) were injected into intact (n = 7) and vagotomized dogs (n = 7). Both ATP and adenosine induced rapid onset of hypotension without rebound hypertension and tachycardia. After vagotomy, the attenuation of RSNA by ATP was completely abolished and rebound hypertension and tachycardia were observed. Vagotomy did not alter the effect of adenosine on RSNA. It is concluded that ATP-induced hypotension is associated with attenuation of sympathetic efferent nerve activity mediated through vagal afferent pathways. Vagal afferent impulses are thought to be one of the mechanisms that inhibit reflex sympathetic activities, such as rebound hypertension after ATP-induced hypotension. The mechanisms by which adenosine inhibits reflex sympathetic activity are not, however, secondary to vagal afferent involvement and must be multifactorial.

Purinergic signalling in the kidney in health and disease

“…In a recent paper, it was shown that P2X7 receptor antagonism prevented the development of salt-sensitive hypertension and renal injury in Dahl salt-sensitive rats [176]. ATP-induced hypotension is associated with alteration of sympathetic nerve activity mediated through vagal afferent pathways [366]. It has been reported that there is an increase in ATP hydrolysis resulting from an increase in ecto-5′-nucleotidase activity and accumulation of adenosine in the kidney of hypertensive animals [96].…”

Sympathetic innervation of the kidney in health and disease: Emphasis on the role of purinergic cotransmission

“…Hypertension is associated with sympathetic hyperactivity and chronic kidney disease (see Amann and Veelken, 2003). It was suggested that ATP-induced hypotension is associated with attenuation of sympathetic efferent nerve activity mediated through vagal afferent pathways, via reflex activation, and vagal afferent impulses may be one of the mechanisms that inhibit reflex sympathetic activities, such as rebound hypertension after ATP-induced hypotension (Taneyama et al, 1991). The purinergic component of sympathetic cotransmission has been shown to be much increased in spontaneously hypertensive rats (Bulloch and McGrath, 1992;Vidal et al, 1986).…”