Increases in coronary vascular resistance initiated by blockade of CNS GABAergic tone occurs in the hindbrain.
The purpose of this study was to determine the site of action in the CNS responsible for producing picrotoxin-induced sympathetic mediated increase in coronary vascular resistance. To do this, picrotoxin, was administered either into the lateral cerebral ventricle, with the perfusion restricted to the forebrain, or into the fourth ventricle, to perfuse only the hindbrain and spinal cord, in chloralose-anesthetized cats, while monitoring coronary blood flow from the anterior descending branch of the left coronary artery, arterial pressure, heart rate and electrocardiogram (ECG). There was no difference between administration into the forebrain and hind-brain in terms of changes in coronary vascular resistance, ECG, arterial pressure and sinus rate when 600 micrograms of picrotoxin was used. Administration into either area elicited significant increases in coronary vascular resistance, arterial pressure and sinus rate, as well as changes in the ST segment and occasional ventricular tachyarrhythmias. However, a separation of effects was noted between the forebrain and the hindbrain when 200 micrograms of picrotoxin was administered. Administration of this dose into the forebrain did not significantly alter coronary vascular resistance or the ST segment, although significant increases in arterial pressure and sinus rate occurred in these animals. In contrast, administration of this dose into the hindbrain elicited significant increases in coronary vascular resistance, ST segment, arterial pressure and sinus rate. These results indicate that the most sensitive site for eliciting picrotoxin-induced increase in coronary vascular lies in the hindbrain.
Segal
S A
SA
Department of Pharmacology, Georgetown University, School of Medicine, Washington, DC 20007.
Gillis
R A
RA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D018756:GABA Antagonists; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*
D018756:GABA Antagonists; D010852:Picrotoxin