Effects of Cyclic Nucleotides and Glipizide on the Cardiovascular Response of Baclofen in the Rats

흰쥐의 척수에서 Cyclic Nucleotides 및 Glipizide가 Baclofen의 심혈관반응에 미치는 영향

  • Koh, Hyun-Chul (Department of Pharmacology, College of Medicine, Hanyang University) ;
  • Ha, Ji-Hee (Department of Pharmacology, College of Medicine, Hanyang University) ;
  • Shin, In-Chul (Department of Pharmacology, College of Medicine, Hanyang University)
  • 고현철 (한양대학교 의과대학 약리학교실) ;
  • 하지희 (한양대학교 의과대학 약리학교실) ;
  • 신인철 (한양대학교 의과대학 약리학교실)
  • Published : 1997.12.21

Abstract

The purpose of present study is to investigate the influence of a spinal gamma-aminobutyric acid B($GABA_B$) receptor on a central regulation of blood pressure(BP) and heart rate(HR), and to define its mechanism in the spinal cord. In urethane-anesthetized, d-tubocurarine-paralyzed and artificially ventilated male Sprague-Dawley rats, intrathecal administration of drugs were carried out using injection cannula(33-gauge stainless steel) through the guide cannula(PE 10) which was inserted intrathecally at lower thoracic level through the puncture of a atlantooccipital membrane. Intrathecal injection of an $GABA_B$ receptor agonist, baclofen(30, 60, 100 nmol) decreased both BP and HR dose-dependently. Pretreatment with 8-bromo-cAMP(50 nmol), a cAMP analog, or glipizide(50 nmol), a ATP-sensitive $K^+$ channel blocker, attenuated the depressor and bradycardic effects of baclofen(100 nmol), but not with 8-bromo-cGMP(50 nmol), a cGMP analog. These results suggest that the $GABA_B$ receptor in the spinal cord plays an inhibitory role in central cardiovascular regulation and that this depressor and bradycardic actions are mediated by the decrease of cAMP via the inhibition of adenylate cyclase and the opening of $K^+$ channel.

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