ANF-RGC is the prototype membrane guanylate cyclase, both the receptor and the signal transducer of the hormones ANF and BNP. After binding them at the extracellular domain it, at its intracellular domain, signals activation of the C-terminal catalytic module and accelerates production of the second messenger, cyclic GMP. This, in turn, controls the physiological processes of blood pressure, cardiovascular function, and fluid secretion, and others: metabolic syndrome, obesity and apoptosis. What is the biochemical mechanism by which this single molecule controls these diverse processes, explicitly of the blood pressure regulation is the subject of the present study. In line with the concept that the structural modules of ANF-RGC are designed to respond to more than one, yet distinctive signals, the study demonstrates the construction of a novel ANF-RGC-In-gene-669WTAPELL675 mouse model. Through this model, the study establishes that 669WTAPELL675 is a vital ANF signal transducer motif of the guanylate cyclase. Its striking physiological features linked with their biochemistry are that (1) it controls the hormonally-dependent cyclic GMP production in the kidney and the adrenal gland; (3) its deletion causes hypertension, and (3) cardiac hypertrophy; and (4) these mice show higher levels of the plasma aldosterone. For the first time, a mere 7-amino acid encoded motif of the mouse gene has been directly linked with the physiological control of the blood pressure regulation, a detailed biochemistry of this linkage has been established and a model for this linkage has been offered.