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 alpha 2-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 alpha 2-adrenergic receptor restraint of both
norepinephrine release and
catecholamine synthesis in juvenile SHR.