IN-VIVO HYPOTHALAMIC RELEASE AND SYNTHESIS OF CATECHOLAMINES IN SPONTANEOUSLY HYPERTENSIVE RATS

Juvenile spontaneously hypertensive rats (SHR) have higher plasma leve ls of catechols and markedly larger catechol responses to yohimbine th an do normotensive Wistar-Kyoto rats, indicating increased sympathoadr enal outflow and increased alpha2-adrenergic receptor-mediated restrai nt 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 nore pinephrine, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dih ydroxyphenylacetic acid in conscious animals before and after yohimbin e injection (1 mg/kg IV) beginning 24 hours after probe implantation. Catecholamine synthesis was examined from elevations of 3,4-dihydroxyp henylalanine 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 (265 9+/-369 versus 1890+/-144 pg/mL), and dihydroxyphenylacetic acid (46 3 12+/-5512 versus 13 187+/-1963 pg/mL) levels and markedly larger incre ases in 3,4-dihydroxyphenylalanine levels after NSD-1015 than Wistar-K yoto rats. In juveniles, SHR had larger proportionate increments in mi crodialysate norepinephrine levels after yohimbine than Wistar-Kyoto r ats (85% versus 25%). Although juvenile SHR and Wistar-Kyoto rats had similar NSD-1015-elicited increments in 3,4-dihydroxyphenylalanine lev els, systemic yohimbine enhanced the NSD-1015-elicited 3,4-dihydroxyph enylalanine elevations in juvenile SHR but not in Wistar-Kyoto rats. T hese findings suggest augmented norepinephrine release and catecholami ne synthesis in the posterolateral hypothalamus of adult SHR and augme nted alpha2-adrenergic receptor restraint of both norepinephrine relea se and catecholamine synthesis in juvenile SHR.