title: In vivo hypothalamic release and synthesis of catecholamines in spontaneously hypertensive rats.
abstract: 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.
authors.affiliation: Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Md. 20892.
authors.forename: K
authors.initials: K
authors.lastname: Pacák
authors.forename: G
authors.initials: G
authors.lastname: Yadid
authors.forename: G
authors.initials: G
authors.lastname: Jakab
authors.forename: J W
authors.initials: JW
authors.lastname: Lenders
authors.forename: I J
authors.initials: IJ
authors.lastname: Kopin
authors.forename: D S
authors.initials: DS
authors.lastname: Goldstein
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism*; D002396:Catechols / Q000378:metabolism; D003956:Dialysis; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007267:Injections; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D002396:Catechols; D006834:Hydrazines; D015016:Yohimbine; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine