Altered basal release and pressor effect of L-DOPA in the rostral ventrolateral medulla of spontaneously hypertensive rats.
1. Transmitter-like L-DOPA functions as a tonic to produce postsynaptic cardiopressor responses in the rostral ventrolateral medulla (RVLM) of rats. We attempted to clarify whether a transmitter-like L-DOPA system is altered in the RVLM of spontaneously hypertensive rats (SHR) to maintain the hypertension. 2. By microdialysis of left RVLM area, the basal L-DOPA release was higher in SHR than in Wistar-Kyoto (WKY) rats. This release was partially inhibited by tetrodotoxin (TTX, 1 mu mol/L) to a similar degree in both strains. TTX-sensitive L-DOPA release was higher in SHR than in WKY. 3. L-DOPA (10-600 ng) and L-glutamate (10-300 ng) microinjected into left RVLM produced dose-dependent hypertension and tachycardia. Pressor but not tachycardiac responses to L-DOPA at lower doses were slightly greater in SHR than in WKY, whereas no difference to L-glutamate was observed in either strain. 4. In RVLM regions, there was no difference of tyrosine hydroxylase activity in SHR or WKY; however, L-aromatic amino acid decarboxylase activity was lower in SHR than in WKY. 5. Enhanced presynaptic neuronal L-DOPA release, including a decrease in decarboxylation and sensitization of postsynaptic pressor sites to L-DOPA in RVLM, may be involved in the maintenance of hypertension in SHR.
Yue
J L
JL
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Miyamae
T
T
Ueda
H
H
Misu
Y
Y
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007980:Levodopa / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000201:enzymology / Q000378:metabolism*; D017551:Microdialysis; D008845:Microinjections; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013779:Tetrodotoxin / Q000494:pharmacology; D014443:Tyrosine / Q000096:biosynthesis; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D018698:Glutamic Acid; D014443:Tyrosine; D013779:Tetrodotoxin; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases