TY - JOUR
T1 - In vivo hypothalamic release and synthesis of catecholamines in spontaneously hypertensive rats
AU - Pacák, Karel
AU - Yadid, Gal
AU - Jakab, Gabor
AU - Lenders, Jacques W.M.
AU - Kopin, Irwin J.
AU - Goldstein, David S.
PY - 1993/10
Y1 - 1993/10
N2 - Juvenile spontaneously hypertensive rats (SHR) have higher plasma levels of catechols and markedly larger catechol responses to yohimbine than do normotensive Wistar-Kyoto rats, indicating increased sympathoadrenal outflow and increased α2-adrenergic receptor-mediated restraint of peripheral catecholamine release during hypertension development in SHR. Yohimbine-induced catecholamine release and metabolism in the posterolateral hypothalamus of the brain were assessed in juvenile (6 to 7 weeks) and adult (15 to 16 weeks) SHR and Wistar-Kyoto rats. In vivo microdialysis was used to obtain samples for measurements of norepinephrine, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid in conscious animals before and after yohimbine injection (1 mg/kg IV) beginning 24 hours after probe implantation. Catecholamine synthesis was examined from elevations of 3,4-dihydroxyphenylalanine levels after probe perfusion with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. In adults, SHR had higher dialysate norepinephrine (277±38 versus 181±35 pg/mL), dihydroxyphenylglycol (3260±509 versus 2231±201 pg/mL), methoxyhydroxyphenylglycol (2659±369 versus 1890±144 pg/mL), and dihydroxyphenylacetic acid (46 312±5512 versus 13 187±1963 pg/mL) levels and markedly larger increases in 3,4-dihydroxyphenylalanine levels after NSD-1015 than Wistar-Kyoto rats. In juveniles, SHR had larger proportionate increments in microdialysate norepinephrine levels after yohimbine than Wistar-Kyoto rats (85% versus 25%). Although juvenile SHR and Wistar-Kyoto rats had similar NSD-1015-elicited increments in 3,4-dihydroxyphenylalanine levels, systemic yohimbine enhanced the NSD-1015-elicited 3,4-dihydroxyphenylalanine elevations in juvenile SHR but not in Wistar-Kyoto rats. These findings suggest augmented norepinephrine release and catecholamine synthesis in the posterolateral hypothalamus of adult SHR and augmented α2-adrenergic receptor restraint of both norepinephrine release and catecholamine synthesis in juvenile SHR.
AB - Juvenile spontaneously hypertensive rats (SHR) have higher plasma levels of catechols and markedly larger catechol responses to yohimbine than do normotensive Wistar-Kyoto rats, indicating increased sympathoadrenal outflow and increased α2-adrenergic receptor-mediated restraint of peripheral catecholamine release during hypertension development in SHR. Yohimbine-induced catecholamine release and metabolism in the posterolateral hypothalamus of the brain were assessed in juvenile (6 to 7 weeks) and adult (15 to 16 weeks) SHR and Wistar-Kyoto rats. In vivo microdialysis was used to obtain samples for measurements of norepinephrine, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid in conscious animals before and after yohimbine injection (1 mg/kg IV) beginning 24 hours after probe implantation. Catecholamine synthesis was examined from elevations of 3,4-dihydroxyphenylalanine levels after probe perfusion with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. In adults, SHR had higher dialysate norepinephrine (277±38 versus 181±35 pg/mL), dihydroxyphenylglycol (3260±509 versus 2231±201 pg/mL), methoxyhydroxyphenylglycol (2659±369 versus 1890±144 pg/mL), and dihydroxyphenylacetic acid (46 312±5512 versus 13 187±1963 pg/mL) levels and markedly larger increases in 3,4-dihydroxyphenylalanine levels after NSD-1015 than Wistar-Kyoto rats. In juveniles, SHR had larger proportionate increments in microdialysate norepinephrine levels after yohimbine than Wistar-Kyoto rats (85% versus 25%). Although juvenile SHR and Wistar-Kyoto rats had similar NSD-1015-elicited increments in 3,4-dihydroxyphenylalanine levels, systemic yohimbine enhanced the NSD-1015-elicited 3,4-dihydroxyphenylalanine elevations in juvenile SHR but not in Wistar-Kyoto rats. These findings suggest augmented norepinephrine release and catecholamine synthesis in the posterolateral hypothalamus of adult SHR and augmented α2-adrenergic receptor restraint of both norepinephrine release and catecholamine synthesis in juvenile SHR.
KW - 3,4-dihydroxyphenylacetic acid
KW - DOPA
KW - Hypertension
KW - Methoxyhydroxyphenylglycol
KW - Receptors, adrenergic
KW - Sympathetic nervous system
UR - http://www.scopus.com/inward/record.url?scp=0027493380&partnerID=8YFLogxK
U2 - 10.1161/01.hyp.22.4.467
DO - 10.1161/01.hyp.22.4.467
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C2 - 8406651
AN - SCOPUS:0027493380
SN - 0194-911X
VL - 22
SP - 467
EP - 478
JO - Hypertension
JF - Hypertension
IS - 4
ER -