Hypertension, Vol 11, 427-432, Copyright © 1988 by American Heart Association
E Mills and JW Bruckert
To identify genetic factors linked obligatorily to hypertension in the rat,
pithed spontaneously hypertensive rats (SHR) were compared with genetically
similar (Wistar-Kyoto rats; WKY) and different (Sprague- Dawley)
normotensive strains. The only variables that distinguished SHR from both
WKY and Sprague-Dawley rats were a greater maximum pressor response to
electrical stimulation of sympathetic outflow and decreased sensitivity to
submaximal doses of the alpha 1-adrenergic agonist methoxamine (i.e.,
higher ED50). SHR had in common with Sprague-Dawley rats basal blood
pressure after pithing plus adrenalectomy and the maximum pressor response
to methoxamine; both these values were higher than those in WKY. All
strains demonstrated equal sensitivity of the vasoconstrictor response to
endogenous norepinephrine released by electrical simulation at submaximal
frequency, even though sensitivity to the alpha 1-adrenergic receptor
agonist was lower in SHR. The alpha 2-adrenergic receptor antagonist
rauwolscine attenuated the pressor response to electrical stimulation in
SHR and WKY but increased it in Sprague-Dawley rats. The alpha 1-adrenergic
receptor antagonist prazosin attenuated the response more in SHR and WKY
than in Sprague- Dawley rats. We conclude that 1) sympathetic hyperactivity
is linked obligatorily to hypertension in SHR; 2) increased basal blood
pressure and noradrenergic vasoconstrictor response are present in SHR, but
they are not obligatorily linked to hypertension; 3) feedback inhibition of
norepinephrine release is comparable in SHR or WKY and poorly developed
compared with that in Sprague-Dawley rats; 4) decreased sensitivity of the
pressor response to stimulation of vascular alpha 1-adrenergic receptors in
SHR compensates partially for increased sympathetic activity or
hyperinnervation, or both.
ARTICLES
Pressor mechanisms linked obligatorily to spontaneous hypertension in the rat
Department of Pharmacology, Duke University Medical School, Durham, North Carolina.
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