Effects of captopril on [3H]-norepinephrine release in rat central nervous system.
1. The present study was performed to investigate the effects of captopril (an angiotensin converting enzyme inhibitor, ACE-I) on noradrenergic transmission in the rat central nervous system. 2. Slices of rat hypothalamus and medulla oblongata were prepared and prelabelled with [3H]-norepinephrine. Slices were continuously superfused with Krebs-Ringer solution, and electrical stimulation (1 Hz) was performed. 3. Captopril significantly inhibited the stimulation-evoked [3H]-norepinephrine release from rat hypothalamic slices in a dose-dependent manner (S2/S1 ratio: control 0.904 +/- 0.025, n = 6, captopril 1 x 10(-5) mol/L 0.617 +/- 0.043, n = 6, P < 0.05, captopril 5 x 10(-5) mol/L 0.547 +/- 0.037, n = 6, P < 0.05). However, the basal release of [3H]-norepinephrine was not affected by captopril. 4. Captopril also reduced the stimulation-evoked [3H]-norepinephrine release in the medulla oblongata (S2/S1 ratio: control 0.878 +/- 0.018, n = 6, captopril 3.3 x 10(-5) mol/L 0.624 +/- 0.046, n = 6, P < 0.05). 5. These results show that captopril might inhibit the stimulation-evoked norepinephrine release in rat hypothalamus and medulla oblongata. Although the precise mechanisms underlying the neurosuppressive effect of captopril are still uncertain, the finding suggests that the inhibition of noradrenergic transmission might be related to the central action of the ACE-I.
Tsuda
K
K
Neurochemistry Research Laboratory New York University Medical Center, New York, USA.
Tsuda
S
S
Nishio
I
I
Masuyama
Y
Y
Goldstein
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004558:Electric Stimulation; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D009638:Norepinephrine