ALPHA(1) ADRENERGIC RECEPTOR-INDUCED C-FOS GENE-EXPRESSION IN RAT AORTA AND CULTURED VASCULAR SMOOTH-MUSCLE CELLS

While growth of blood vessels is important in hypertension, relatively little is known about the contribution of catecholamines. Using isola ted rat aorta and cultured smooth muscle cells, we examined adrenergic stimulation of gene expression. Phenylephrine, a selective alpha(1) a drenergic receptor agonist, caused a rapid and transient increase in c -fos mRNA accumulation which was inhibited by prazosin, an alpha(1) re ceptor antagonist. Similarly, phenylephrine stimulated c-jun and c-myc mRNA accumulation. Chlorethylclonidine, a compound which irreversibly blocks alpha(1B) receptors, completely blocked the phenylephrine-indu ced increase in c-fos mRNA. RNase protection experiments demonstrated that rat aorta prominently expressed mRNA for alpha(1B) and alpha(1A/D ) receptors. Phenylephrine-induced c-fos mRNA was partially inhibited by H-7, a protein kinase C inhibitor, and by nifedipine, a Ca2+ channe l blocker; these two compounds together had additive effects. In situ hybridization showed that expression of c-fos mRNA induced by phenylep hrine was localized to aorta's medial layer. These results suggest tha t alpha, receptor-induced increase in c-fos mRNA in aorta is mediated by a chlorethylclonidine-sensitiue receptor subtype signaling via incr easing intracellular Ca2+ concentrations and activating protein kinase C.