Hypertension, Vol 14, 44-53, Copyright © 1989 by American Heart Association
T Hano and J Rho
We examined the overflow of endogenous norepinephrine with electrical
stimulation, the associated pressor response, and rate of initial neuronal
uptake of [3H]norepinephrine in perfused mesenteric arteries of 7- and
13-week-old spontaneously hypertensive rats (SHR) and Wistar- Kyoto (WKY)
rats. The tissues of two rats, a spontaneously hypertensive and a WKY
control rat, were simultaneously processed and subjected to the same
electrical stimulation. Both absolute and fractional overflow of endogenous
norepinephrine during periarterial nerve stimulation (5 and 10 Hz for 1
minute) in the tissue of 7-week-old SHR was significantly greater whereas
overflow of 13-week-old SHR was equivalent as compared with that of the
age-matched WKY rats. The tissue content of norepinephrine was 20-25%
higher in SHR of both ages. There was significantly enhanced
[3H]norepinephrine uptake in the tissues of young SHR, but no difference
was observed in the older SHR. The pressor response to periarterial nerve
stimulation was significantly enhanced in 7-week-old SHR and much more so
at the older age as compared with the WKY control rats. Exogenous
norepinephrine dose-response curves in the tissues of 7-week-old SHR
exhibited a parallel leftward shift, characteristic of a change in
sensitivity, whereas that of 13-week-old SHR showed a much steeper slope as
compared with the respective WKY control rats. This finding suggests that
in addition to smooth muscle supersensitivity, structural alterations had
occurred in vasculature of 13-week-old SHR. These data indicate that in SHR
both the exocytotic release of norepinephrine and the responsiveness of the
vascular smooth muscle cells are enhanced in the developmental stage of
hypertension whereas smooth muscle supersensitivity to norepinephrine and
nonspecific structural alterations primarily contribute to the maintenance
of hypertension at 13 weeks of age.
ARTICLES
Norepinephrine overflow in perfused mesenteric arteries of spontaneously hypertensive rats
Department of Clinical Pharmacology, School of Medicine, University of Southern California, Los Angeles 90033.
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