A seven amino acid peptide (PEP7) is encoded within a short open reading frame (sORF) within exon 2 (E2) in the 5'-leader sequence (5'LS) upstream of the rat angiotensin 1a-receptor (rAT_1aR) mRNA. A chemically synthesized PEP7 markedly inhibited angiotensin II (Ang II)-induced Erk1/2 activation in cells by 62% vs. a scrambled PEP7 (sPEP7) [pErk1/2/Erk1/2 (AU): Ang II, 1.000±0.0, Ang II+PEP7, 0.3812±0.086, Ang II+sPEP7, 1.069±0.18; n=3]. Under these conditions, PEP7 had no effect on Ang II-stimulated inositol-trisphosphate production. PEP7 also had no effect on EGF- and PMA-induced Erk1/2 activation, suggesting PEP7 selectively inhibits AT_1aR-mediated Erk1/2 signaling. PEP7 i.c.v. inhibited Ang II-induced saline intake but had no effect on water intake in male and female rats indicating PEP7 also selectively inhibits the Ang II-Erk1/2 pathway in vivo since saline drinking is Erk1/2-mediated while water drinking is not. PEP7 inhibition of Ang II-induced saline ingestion was rapidly reversed by a subsequent i.c.v. injection of an oxytocin antagonist suggesting when PEP7 blocks Ang II-stimulated Erk1/2 activation, animals no longer ingest saline to balance the continued water intake, due to release of oxytocin and its subsequent inhibitory effects on saline drinking. PEP7 also attenuated Ang II-induced increases in arterial pressure by 35% when compared to sPEP7. Thus, we have identified a novel peptide encoded within the rAT_1aR E2 that selectively inhibits Erk1/2 activation resulting in physiological consequences for sodium ingestion and arterial pressure that has implications for treating sodium-sensitive diseases like hypertension and kidney disease.