Comparison of the cardiovascular effects of intravenously administered GABA, THIP, and isoguvacine in the anesthetized rat

Abstract

AbstractMean arterial blood pressure and heart rate were monitored in pentobarbital‐anesthetized rats after intravenous injections of GABA, THIP, or isoguvacine‐HCl (all at 0.1–100 mg/kg). GABA produced dose‐dependent hypotension and bradycardia; THIP produced no appreciable effect on either parameter; and isoguvacine produced hypotension, but no marked change in heart rate. The transient hypotension and bradycardia produced by GABA (1 mg/kg) were partially blocked by pretreatment of the animals with bicuculline or bicuculline‐methobromide. After pretreatment with bicuculline or bicuculline‐methobromide, the hypotensive effect of isoguvacine (1 mg/kg) occurred more rapidly (i.e., during the first 5 min, rather than during 5–15 min after injection of isoguvacine). As THIP penetrates the blood‐brain barrier more readily than GABA or isoguvacine, as GABA and isoguvacine exerted more pronounced cardiovascular effects than THIP, and as bicuculline and bicuculline‐methobromide affected the cardiovascular actions of GABA and isoguvacine, it is suggested that activation of peripheral GABA receptors might explain part of the cardiovascular effects produced by intravenously injected GABA. Further study of isoguvacine and its derivatives might lead to the development of hypotensive (antihypertensive) agents that act on peripheral GABA‐ergic systems.