Publisher Summary This chapter presents a remarkable interaction of oxytocin (OT) and atrial natriuretic peptide (ANP) to control not only the intake of salt and water in actions mediated by sodium receptors and baroreceptors but also to control the release of natriuretic hormones from the brain, heart, and vascular system. In the brain, baroreceptor input and input from sodium receptors cause release of ANP, which in turn activates the release of OT. OT and ANP act to inhibit water and salt intake probably by inhibiting the intrahypothalamic release of angiotensin II, whereas the principal mechanism to release ANP from the heart is by OT's activation of its receptors on the heart, particularly in the fight atrium, to trigger the release of ANP. OT acts in the brain and kidney not only by releasing ANP but also by activating nitric acid synthase (NOS). All three transmitters act through cyclic guanosine 3'-5'-monophosphate (cGMP). The OT acts on its receptors to activate NOS causing a further increase in cGMP augmenting the natriuresis and kaliuresis so that the resulting effect is the combination of the increased cGMP induced by OT through NO and ANP by its own action to increase cGMP. The increased electrolyte excretion finally returns the blood volume and extracellular fluid volume to normal levels.