Lq. Chen et al., REGULATION OF VASCULAR SMOOTH-MUSCLE GROWTH BY ALPHA(1)-ADRENOCEPTOR SUBTYPES IN-VITRO AND IN-SITU, The Journal of biological chemistry, 270(52), 1995, pp. 30980-30988
Rat aorta smooth muscle cells which express all three alpha(1)-adrenor
eceptors (alpha(1A), alpha(1B) and alpha(1D)) were used to determine t
he effect of stimulation of alpha(1)-adrenergic receptor subtypes on c
ell growth. ''Combined'' alpha(1)-adrenoreceptor subtype stimulation w
ith norepinephrine alone caused a concentration-dependent, prazosin se
nsitive increase in protein content and synthesis: 48 h of stimulation
at 1 mu M increased cell protein to 216 +/- 40% of time-matched contr
ols (p = 0.008) and RNA to 140 +/- 13% (p = 0.03); protein synthesis i
ncreased to 167 +/- 13% (p < 0.01) after 24 h, Stimulation with norepi
nephrine plus the selective alpha(1A)/alpha(1D) antagonist 5-methylura
pidil produced greater increases in alpha-actin mRNA (270 +/- 40% at 8
h; p = 0.007), total cell protein (220 +/- 45% at 24 h; p = 0.004), a
nd RNA (135 +/- 8% at 24 h; p = 0.01). These effects were prevented by
pretreatment with the selective alpha(1B) antagonist chloroethylcloni
dine. Comparable results were obtained for intact aortae. Stimulation
with norepinephrine plus 5-methylurapidil increased (p < 0.05) tissue
protein, RNA, dry weight, and alpha-actin mRNA; and as in cultured cel
ls, combined stimulation with norepinephrine alone attenuated these re
sponses. By comparison, adventitia (fibroblasts) was unaffected, Remov
al of endothelial cells had no effect. alpha(1B) mRNA decreased by 42
+/- 12% (p = 0.01) in cultured cells during combined alpha(1)-adrenore
ceptor stimulation and by 23 +/- 8% (p = 0.03) for intact aorta. alpha
(1D) and beta-actin mRNA were unchanged in cultured cells, aorta media
, and adventitia. These findings suggest that prolonged stimulation of
chloroethylclonidine-sensitive, possibly alpha(1B)-adrenoreceptors in
duces hypertrophy of arterial smooth muscle cells and that stimulation
of 5-methylurapidil-sensitive, non-alpha(1B)-adrenoreceptors attenuat
es this growth response.