Nitric Oxide (NO) exerts an integrative role as a relatively ubiquitous signaling molecule in the cardiovascular, neurological and immunological systems. Disturbances in its short bioavailability influence the physiology of the organism as a whole and predispose to a large number of pathologies such as hypertension, heart failure, peripheral and central autonomic outflow and the function of immune cells. Here, we report that a proline-rich oligopeptide derived from the brain and from the venom gland of a Brazilian snake reduces the arterial blood pressure of spontaneously hypertensive rats but not of normotensive animals. This effect is independent on Angiotensin Converting Enzyme (ACE) inhibition and bradykinin potentiation. In vitro, this peptide specifically binds to argininosuccinate synthase and increases by 30% the synthesis of L-arginine which plays a pivotal role in nitric oxide production. In molar terms, BPP-10c is the most powerful natural and long-lasting anti-hypertensive substance acting in spontaneously hypertensive rats.