[Alteration of neurotransmitters in the cerebrospinal fluid in SHRSP rats due to long-term administration of clonidine].
BACKGROUND
Clonidine, an alpha2-adrenoreceptor and imidazoline L receptor agonist, is commonly used in the treatment of hypertension. We evaluated the central hypotensive effect of long-term oral administration of clonidine.


METHODS
Clonidine was administered to stroke-prone spontaneously hypertensive rats (SHRSP) of four to twenty weeks of age. Cerebrospinal fluid (CSF) was collected via the cisterna magna every two weeks, from eight weeks of age, from clonidine treated SHRSPs, age-matched normotensive Wistar Kyoto (WKY) rats and un-treated SHRSPs. Amino acid neurotransmitters and monoamine neurotransmitters in the samples were measured by high performance liquid chromatography with electro-chemical detectors.


RESULTS
The levels of norepinephrine, dopamine and serotonin were significantly higher, while taorine was significantly lower in the SHRSPs than in WKY rats. Long-term clonidine administration decreased the levels of norepinephrine, dopamine, serotonin, GABA and taurine. The levels of excitatory amino acids, however, were unaffected by clonidine administration. The levels of metabolites of norepinephrine increased, but those of dopamine and serotonin decreased.


CONCLUSIONS
These results suggest that the presynaptic inhibition of norepinephrine release from norepinephrine neurons, accompanied by postsynaptic inhibition of excitatory and inhibitory neurons modulate clonidine-induced hypotension.
Iwasaki
Eiji
E
Department of Anesthesiology, Kinki University School of Medicine, Osaka-Sayama 589-8511.
Takasugi
Yoshihiro
Y
Koga
Yoshihisa
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage* / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid*; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D015306:Biogenic Monoamines; D018377:Neurotransmitter Agents; D003000:Clonidine; D009638:Norepinephrine