Loss of tonic neuronal activity to release L-DOPA in the caudal ventrolateral medulla of spontaneously hypertensive rats.
Experiments were designed to clarify whether a tonic L-DOPA system is altered in the caudal ventrolateral medulla (CVLM) of adult spontaneously hypertensive rats (SHR), compared to age-matched Wistar-Kyoto rats (WKY). By microdialysis in CVLM, basal L-DOPA release was constantly detectable and was lower in SHR than that in WKY. This release was reduced by tetrodotoxin perfusion (1 microM) in WKY to a basal level in SHR, whereas no modification occurred with tetrodotoxin in SHR. No difference of tyrosine hydroxylase and DOPA decarboxylase activities in the CVLM region was seen between the two strains. By microinjections into depressor sites of CVLM, L-DOPA (10-300 ng) or L-glutamate (3-300 ng) elicited dose-dependent depressor and bradycardic responses and greater depressor responses to both amino acids were seen at high doses in SHR, compared to WKY. Tonic neuronal activity to release L-DOPA is lost in the CVLM of adult SHR and this loss may contribute to maintenance of hypertension in SHR.
Miyamae
T
T
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Yue
J L
JL
Okumura
Y
Y
Goshima
Y
Y
Misu
Y
Y
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013779:Tetrodotoxin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D013779:Tetrodotoxin; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases