title: Systematic understanding of acute effects of intravenous guanfacine on rat carotid sinus baroreflex-mediated sympathetic arterial pressure regulation.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan. Electronic address: torukawa@ncvc.go.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Kawada
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Turner
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukumitsu
authors.affiliation: Division of Cardiology, Department of Medicine, Faculty of Medicine, Kinki University, Osaka 589-8511, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
mesh_terms: D061605:Administration, Intravenous; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D002346:Carotid Sinus / Q000187:drug effects* / Q000502:physiology; D016316:Guanfacine / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D016316:Guanfacine
keywords: Alpha-2 agonist; Carotid sinus baroreflex; Guanfacine; Open-loop systems analysis; Sympathetic nerve activity