Abstract

The contribution of the alpha-1B adrenergic receptor (AR) to vascular smooth muscle contraction has been assessed using a combination of immunological, molecular biological and pharmacological approaches. A subtype-selective antibody detectedalpha-1B immunoreactivity in the medial layer of the aorta, caudal, femoral, iliac, mesenteric resistance, renal and superior mesenteric arteries. Receptor protection assays and antisense oligonucleotides were used to assess the contribution of thealpha-1B AR to contraction. Thealpha-1B AR was implicated in mediating the phenylephrine-induced contraction of the mesenteric resistance artery. The alpha-1D AR was implicated in mediating the contraction of the aorta, femoral, iliac and superior mesenteric arteries. Similarly, the alpha-1A AR was implicated in mediating contraction of the caudal and renal arteries. In vivo application of antisense oligonucleotides targeted to the translational start site of the alpha-1B AR had no effect on the phenylephrine-induced contraction of the femoral or renal arteries. In contrast, antisense oligonucleotides directed against the alpha-1D AR significantly inhibited the phenylephrine response in the femoral artery but had no effect on the renal artery. Application of alpha-1A AR antisense oligonucleotides inhibited the contraction of the renal artery without effect on the femoral artery. These data show that (1)alpha-1B AR immunoreactivity is widely distributed in the same peripheral arteries in which previous studies detected its mRNA, and (2) despite this distribution, receptor protection and antisense oligonucleotide studies indicate that thealpha-1B AR mediates the contraction of only the mesenteric resistance artery.