Interactions of angiotensin II and atrial natriuretic peptide in the brain: fish to rodent.

The brain peptides atrial natriuretic peptide (ANP) and angiotensin II (AngII) have antagonistic actions centrally that have evolved to play an important role in maintaining the homeostasis of fluid volume and electrolytes. This paper discusses the possible evolution of these functions as viewed through studies on fish and rats. In the euryhaline teleost fish, the major form of ANP is CNP. CNP is important for the adaptation of fish in sea water to water with lower salinity (50% SW). The concentration of CNP in the hypothalamus (HTS-CNP) of toadfish is significantly increased when the fish moves from SW to 50% SW. Interestingly, the plasma CNP concentrations of these fish go in the opposite direction to the brain CNP. Plasma CNP is reduced 24 hrs and 10 days after the fish has been in 50% SW. We postulate that the increased hypothalamic CNP is correlated with an increase in hypothalamic dopamine turnover. Dopamine is the main inhibitory factor for the release of prolactin. In sea-water-adapted fish, prolactin plasma levels are low. In 50% SW, the levels are increased. Extracts of fish-brain CNP caused an increase in urinary sodium and volume, indicating the natriuretic action of CNP. In contrast to CNP, hypothalamic AngII was decreased during adaptation to 50% SW. Thus, CNP and AngII in the brain have opposite actions in fish which aid in their survival in adapting to different salinities. This implies that the hormones evolved as sodium/osmoregulatory peptides, not volume-regulatory peptides. In moving from an aquatic to a terrestrial environment, ANP further evolved in mammals as a volume-regulating hormone while retaining its sodium-regulating properties. In the brain the antagonism between the peptides is apparent in many actions, but when volume is changed both peptides are increased. This is in contrast to plasma ANP and plasma AngII, which have opposite actions during hemorrhage. Plasma AngII is increased and plasma AnP is decreased after blood volume loss. Brain ANP counteracts the thirst-inducing and volume-restoring roles of brain AngII in mammals. By these actions, the brain peptides play significant roles in maintaining volume and electrolyte homeostasis.