Toru Kawada1, Shuji Shimizu2, Michael J Turner2, Masafumi Fukumitsu2, Hiromi Yamamoto3, Masaru Sugimachi2. 1. Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan. Electronic address: torukawa@ncvc.go.jp. 2. Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan. 3. Division of Cardiology, Department of Medicine, Faculty of Medicine, Kinki University, Osaka 589-8511, Japan.
Abstract
AIMS: To assess the acute effects of intravenous guanfacine, an α2A-adrenergic agonist, on sympathetic outflow from the central nervous system and on sympathetic arterial pressure (AP) response. MAIN METHODS: In anesthetized Wistar Kyoto rats, carotid sinus baroreceptor regions were isolated. Changes in electrical sympathetic nerve activity (SNA) and AP in response to a baroreceptor pressure input were examined before and after an intravenous administration of a high dose (100μg/kg, n=7) or a low dose (20μg/kg, n=5) of guanfacine. KEY FINDINGS: The higher dose of guanfacine significantly narrowed the range of the AP response (86.8±6.4 to 38.4±12.9mmHg, P<0.01) but increased the minimum AP (79.3±7.5 to 93.2±8.7mmHg, P<0.05). In the neural arc, guanfacine reduced both the response range (90.4±2.3 to 33.4±10.7%, P<0.01) and the minimum SNA (11.4±1.9 to 2.6±1.5%, P<0.01). In the peripheral arc, guanfacine increased the intercept (67.6±7.1 to 92.8±8.5mmHg, P<0.01) without a significant effect on the slope. The lower dose of guanfacine weakened the effects on both the neural and peripheral arcs. SIGNIFICANCE: Guanfacine suppressed SNA without a significant reduction of AP, which may be attributable to the peripheral vasoconstrictive effect. Reducing the dose of acutely administered intravenous guanfacine does not aid in separating the central sympathoinhibitory effect from the peripheral vasoconstrictive effect on AP in anesthetized rats in vivo.
AIMS: To assess the acute effects of intravenous guanfacine, an α2A-adrenergic agonist, on sympathetic outflow from the central nervous system and on sympathetic arterial pressure (AP) response. MAIN METHODS: In anesthetized Wistar Kyoto rats, carotid sinus baroreceptor regions were isolated. Changes in electrical sympathetic nerve activity (SNA) and AP in response to a baroreceptor pressure input were examined before and after an intravenous administration of a high dose (100μg/kg, n=7) or a low dose (20μg/kg, n=5) of guanfacine. KEY FINDINGS: The higher dose of guanfacine significantly narrowed the range of the AP response (86.8±6.4 to 38.4±12.9mmHg, P<0.01) but increased the minimum AP (79.3±7.5 to 93.2±8.7mmHg, P<0.05). In the neural arc, guanfacine reduced both the response range (90.4±2.3 to 33.4±10.7%, P<0.01) and the minimum SNA (11.4±1.9 to 2.6±1.5%, P<0.01). In the peripheral arc, guanfacine increased the intercept (67.6±7.1 to 92.8±8.5mmHg, P<0.01) without a significant effect on the slope. The lower dose of guanfacine weakened the effects on both the neural and peripheral arcs. SIGNIFICANCE: Guanfacine suppressed SNA without a significant reduction of AP, which may be attributable to the peripheral vasoconstrictive effect. Reducing the dose of acutely administered intravenous guanfacine does not aid in separating the central sympathoinhibitory effect from the peripheral vasoconstrictive effect on AP in anesthetized rats in vivo.