Sympathoadrenomedullary hyper-responsiveness to yohimbine in juvenile spontaneously hypertensive rats.
We examined responses of arterial plasma levels of the sympathetic neurotransmitter, norepinephrine (NE), of the adrenomedullary hormone, epinephrine (E), and of the intraneuronal NE metabolite, dihydroxyphenylglycol (DHPG), after intravenous administration of the alpha-2 adrenoceptor antagonist, yohimbine, in conscious, freely-moving juvenile (4-week old) or mature (12-week old) rats with spontaneous hypertension (SHRs) and their normotensive Wistar-Kyoto (WKY) controls. Mature SHRs and WKY rats had similar levels of plasma catechols at rest, whereas juvenile SHRs had significantly higher levels of NE (400 +/- 109 (SD) vs 233 +/- 62 pg/ml), E (371 +/- 168 vs 148 +/- 67 pg/ml), and DHPG (800 +/- 147 vs 589 +/- 54 pg/ml). After yohimbine, average responses of NE in the juvenile SHRs were more than 5 times, of E more than 7 times, and of DHPG more than 11 times those of the juvenile WKY rats. The responses of plasma catechols to yohimbine were not excessive in mature 12-week old SHRs. The results demonstrate increased sympathoadrenomedullary activity at rest and markedly enhanced sympathoadrenomedullary responsiveness to yohimbine in juvenile but not mature SHRs and are consistent with the hypothesis that early in the development of hypertension in this laboratory animal model there is an abnormal dependence on central neural alpha-2 adrenoceptors as part of an incompletely successful compensatory mechanism for limiting sympathetic outflow.
Szemeredi
K
K
Intramural Research Program, National Institute of Neurological and Communicative Disorders and Stroke.
Bagdy
G
G
Stull
R
R
Keiser
H R
HR
Kopin
I J
IJ
Goldstein
D S
DS
D000313:Adrenal Medulla / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D000375:Aging; D000818:Animals; D004837:Epinephrine / Q000097:blood / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000502:physiology; D013045:Species Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology*
D015016:Yohimbine; D009638:Norepinephrine; D004837:Epinephrine