In vivo hypothalamic release and synthesis of catecholamines in spontaneously hypertensive rats

Karel Pacák, Gal Yadid, Gabor Jakab, Jacques W.M. Lenders, Irwin J. Kopin, David S. Goldstein

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish
Pages (from-to)467-478
Number of pages12
Issue number4
StatePublished - Oct 1993
Externally publishedYes


  • 3,4-dihydroxyphenylacetic acid
  • DOPA
  • Hypertension
  • Methoxyhydroxyphenylglycol
  • Receptors, adrenergic
  • Sympathetic nervous system


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