Oxygen modulates alpha(1B)-adrenergic receptor gene expression by arterial but not venous vascular smooth muscle

Blood and tissue O-2 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. After exposure of cultured aortic (in vitro) SMC to 3% O-2 for 8 h, alpha(1B) mRNA increased to 523% (P = 0.02) of control cells (21% O-2) and to 205% (P = 0.04) in in situ organ-cultured aortic SMC. In vivo hypoxic hypoxia (10% inspired O-2) similarly increased aortic SMC alpha(1B) mRNA 180% (P = 0.02). In contrast, alpha(1D), alpha-actin and beta-actin mRNA levels were not changed in aortic SMC by low O-2 in the in vitro, in situ, or in vivo models. Unlike aortic SMC, vena caval SMC alpha(1B) mRNA expression did not change with low-O-2 exposure in vitro or in vivo, nor did alpha(1D), alpha-actin or beta-actin mRNA. Aortic SMC alpha(1B) transcription rate increased 360% (P = 0.02), whereas alpha(1D), alpha-actin, and beta-actin transcription was unchanged. Neither alpha(1B) nor alpha(1D) mRNA stability was altered by low-O-2 exposure. Total alpha(1)-adrenoceptor density ([H-3]prazosin binding) increased 12% (P = 0.04) after 24 h of 3% O-2. 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 aortic SMC to 24 h of 3% O-2 increased the maximum response of norepinephrine-evoked elevations in intracellular Ca2+ as measured using fura 2. Low O-2 did not change responses to another G protein-coupled receptor, angiotensin II. These data suggest that reduced O-2, during prolonged hypoxemia or tissue ischemia, may selectively increase expression of functionally coupled alpha(1B)-adrenoceptors in arterial blood vessels.