Modification of cardiovascular responses to spinal GABA(B) receptor stimulation by cAMP and by K(ATP) channel blockade in anaesthetized rats.
1. Intrathecal (i.t.) injection of baclofen (30, 60 and 100 nmol), a GABA(B) receptor agonist, produced a dose-dependent decrease in blood pressure (BP) and heart rate (HR). 2. Pretreatment with 5-aminovaleric acid (50 nmol), a GABA(B) receptor antagonist, blocked the depressor and bradycardic effects of baclofen (100 nmol). 3. Pretreatment with 8-bromo-cAMP (10 nmol), a cAMP analogue, attenuated the depressor and bradycardic effects of baclofen (100 nmol), but not with 8-bromo-cGMP (10 nmol), a cGMP analogue. 4. In addition, pretreatment with glipizide (20 nmol), an ATP-sensitive K+ channel (K(ATP)) blocker, attenuated the depressor and bradycardic effects of baclofen (100 nmol). These results suggest that GABA(B) receptors in the spinal cord have an inhibitory role in the central cardiovascular regulation and that these depressive and bradycardic actions are modified by cAMP and by K(ATP) channel blockade.
Koh
H C
HC
Department of Pharmacology, College of Medicine, Hanyang University, Seoul, South Korea.
Shin
I C
IC
Ha
J H
JH
Paik
D J
DJ
Kang
J S
JS
Lee
C H
CH
D000768:Anesthesia, General; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D018755:GABA Agonists; D015221:Potassium Channels; D018080:Receptors, GABA-B; D000242:Cyclic AMP; D006152:Cyclic GMP; D001418:Baclofen