ANGIOTENSIN-II-INDUCED HYPERTROPHY OF RAT VASCULAR SMOOTH-MUSCLE IS ASSOCIATED WITH INCREASED 18S RIBOSOMAL-RNA SYNTHESIS AND PHOSPHORYLATION OF THE RIBOSOMAL-RNA TRANSCRIPTION FACTOR, UPSTREAM BINDING-FACTOR

Hypertrophy of vascular smooth muscle cells (VSMC) is an important ada ptive response of hypertension. Drug intervention studies have implica ted a role for angiotensin II (A-II) in the mediation of VSMC hypertro phy in vivo, and A-II is a potent hypertrophic agent for VSMC in cultu re. Our laboratory has previously shown that A-II-induced hypertrophy of cultured VSMC is due in part to generalized increases in protein sy nthesis and increased content of rRNA. The aim of the present study wa s to determine if A-II stimulates rRNA gene synthesis and whether the rRNA transcription factor, upstream binding factor (UBF), is involved. Nuclear run-on analysis demonstrated that A-II induced a greater than 5-fold increase in rRNA gene synthesis within 6 h of stimulation. A-I I also stimulated a rapid increase in UBF phosphorylation as well as n ucleolar localization, but no changes in the content of UBF. Phosphoam ino acid analysis showed that phosphorylation occurred only on serine residue(s). Results demonstrate that increased transcription of riboso mal DNA contributes to the A-II-induced increase in protein synthesis and VSMC hypertrophy, and suggest that an important regulatory event i n this pathway may be the phosphorylation and/or nucleolar localizatio n of UBF.