Oxygen modulates [alpha]1b-adrenergic receptor gene expression by
arterial but not venous vascular smooth muscle.
Eckhart, Andrea D., Zhiming Zhu, William J. Arendshorst, and James E.
Faber.
Department of Physiology, The University of North Carolina, Chapel
Hill, NC 27599-7545
APStracts 3:0103H, 1996.
Blood and tissue O2 levels are major determinants of short-term
autoregulatory adjustments in vascular smooth muscle cell (SMC)
tension and may effect long-term alterations in SMC catecholamine
responsiveness. We examined the hypothesis that prolonged hypoxia
altered gene expression of [alpha]1-adrenoceptors. Following exposure
of cultured aorta (in vitro) SMCs to 3% O2 for 8h, [alpha]1B mRNA
increased to 523% (p=0.02) of control cells (21% O2) and to 205%
(p=0.04) in in situ organ cultured aorta SMCs. In vivo hypoxic
hypoxia ( 10% inspired O2) similarly increased aorta SMC [alpha]1B
mRNA 180% (p=0.02). In contrast, [alpha]1D, [alpha]- and [beta]-actin
mRNA levels were not changed in aorta SMCs by low O2 in the in vitro,
in situ or in vivo models. Unlike aorta SMCs, vena cava SMC [alpha]1B
mRNA expression did not change with low O2 exposure in vitro or in
vivo, nor did [alpha]1D, [alpha]- and [beta]-actin mRNA. Aorta SMC
[alpha]1B transcription rate increased 360% (p=0.02), while
[alpha]1D, [alpha]- and [beta]-actin transcription was unchanged.
Neither [alpha]1B or [alpha]1D mRNA stability was altered by low O2
exposure. Total [alpha]1-adrenoceptor density ([3H]prazosin binding)
increased 12% (p=0.04) after 24h of 3% O2. This was associated with a
200% increase (p<0.01) in the chloroethylclonidine (CEC)
-sensitive [alpha]1-adrenoceptor population and no change in CEC
-insensitive [alpha]1-adrenoceptor density. Exposure of aorta SMCs to
24h of 3% O2 increased the maximum response of norepinephrine-evoked
elevations in intracellular Ca2+ as measured using Fura-2. Low O2 did
not change responses to another G-protein coupled receptor,
angiotensin II. These data suggest that reduced O2, during prolonged
hypoxemia or tissue ischemia, may selectively increase expression of
functionally coupled [alpha]1B-adrenoceptors in arterial blood
vessels.
Received 18 December 1995; accepted in final form 4 March 1996.
APS Manuscript Number H1177-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96