We have previously reported that hypertension in the young SHR is associated with an elevation in tissue angiotensinogen (Aogen) and a novel polysomal protein known to stabilize Aogen mRNA. In our current study we determined the role of the mRNA stabilizing protein in the regulation of tissue Aogen expression and mean arterial pressure (MAP) in the SHR utilizing anti-sense oligodeoxynucleotide (AON) inhibition. Three AONs (RNASTAAS1: pos.31-50, RNASTAAS2: pos.21-40, RNASTAAS3: pos.143-162 of the cDNA coding for the polysomal protein) were administered intravenously (dose: 450, 900, and 1800 µg/kg, one dosage per day over three days) in conscious, chronically instrumented male SHRs at the age of 7 weeks. Control SHRs received corresponding scrambled ON sequences (SCR1, SCR2, SCR3). Each animal received the increasing dose schedule. RNASTAAS2 resulted in a reduced expression of the polysomal protein to 21 % (liver), 12 % (brain), 27 % (heart), 18 % (renal cortex), and 22 % (renal medulla) of control. Aogen expression was inhibited to 54 % (liver), 41 % (brain), 68 % (heart), 52 % (renal cortex) and 74 % (renal medulla) compared to control SHRs. Decreases in plasma concentrations of Aogen and plasma renin activities were associated with a significant decrease in MAP from 147 +/- 6 mm Hg (after SCR2) to 106 +/- 4 mmHg after RNASTAAS2. The effects of the two other AONs on MAP were less (RNASTAAS1: -31 mmHg; RNASTAAS3: -16 mmHg) with corresponding decreases in mRNAs coding for Aogen and the polysomal protein. A significant decrease in intracellular concentrations of the polysomal protein accompanied AON inhibition. The magnitude of effects (-15 to -41 mmHg) was comparable to the effects of captopril (100 mg/kg/day for 3 days: -32 mmHg) and an AT1 receptor antagonist (L158809, 1.5 mg/kg/day for 3 days: -36 mmHg). These data suggest an important role of the RNA stabilizing protein for hepatic and extra-hepatic Aogen expression and MAP in the SHR.