Abstract 13295: Interaction Between Neural and Peripheral Effects of Intravenous Guanfacine in Determining Arterial Pressure and Sympathetic Nerve Activity

Abstract

Introduction: Guanfacine is a selective α 2A -adrenergic agonist and suppresses sympathetic nerve activity (SNA) by acting on the central nervous system. In the use of intravenous guanfacine in animal experiments, however, arterial pressure (AP) does not necessarily fall much even when SNA is markedly suppressed. Hypothesis: Intravenous guanfacine may act on peripheral α-adrenergic receptors to increase AP at a given SNA. Methods: To separately assess the neural and peripheral effects of intravenous guanfacine, an open-loop analysis of the carotid sinus baroreflex was performed in 7 anesthetized Wistar-Kyoto rats. Carotid sinus pressure was changed from 60 to 180 mmHg in a staircase manner while steady-state SNA and AP were measured. Effects of intravenous guanfacine (100 μg/kg, bolus) on the baroreflex response was examined. Results: As shown in the figure, the neural arc of the baroreflex approximated a sigmoid curve. Guanfacine reduced the response range of the neural arc from 89.8±2.2% to 32.9±10.9% (P<0.01) and the minimum SNA from 11.6±1.9% to 2.4±1.2% (P<0.01). The peripheral arc of the baroreflex approximated a straight line. Guanfacine increased the intercept from 67.6±7.1 to 92.8±8.5 mmHg (P<0.01) without significantly affecting the slope of AP versus SNA. The operating point of the baroreflex was determined from the intersection between the neural and peripheral arcs on the baroreflex equilibrium diagram (denoted by a double circle). The operating-point SNA decreased from 47.5±6.0% to 13.6±3.9% (P<0.01) whereas the operating-point AP was not decreased significantly (from 114.7±4.3 to 109.0±7.1 mmHg). Conclusions: The operating-point AP and SNA are determined through the interaction between the neural and peripheral effects of intravenous guanfacine. While the operating-point SNA was significantly decreased, the operating-point AP was relatively maintained via the peripheral effect.