Interactions of Angiotensin II and Atrial Natriuretic Peptide in the Brain: Fish to Rodent

Summary and Conclusions

1. In the evolution of the physiological role of ANP, the peptide probably originated as a sodium-regulating hormone for survival in sea water and adapting to changing saline environments.

2. In moving from an aquatic to a terrestrial environment, ANP additionally evolved in mammals as a hormone to counteract volume expansion while retaining its sodium-regulating properties.

3. In the fish brain, the natriuretic-like peptide is CNP, which has evolved as a neuroendocrine hormone. CNP is involved in the control of prolacting release, via dopamine regulation and in the inhibition of thirst mechanism when fish move from sea water into a lower salinity or fresh water environment.

4. In teleost, Ang II brain distribution is similar to rodents. Fish hypothalamic Ang II concentration inversely correlates with the environmental salinity. This supports the role for the hypothalamic Ang II in fish enhanced drinking and mineralocorticoid response while fish adapt to high salinity or sea water.

5. From fish to rodents, ANP in the brain and plasma opposes the actions of Ang II in brain and plasma. The results in rodents, and probably in humans, is that the balance of the two hormones is required to achieve normovolemia.

6. Both brain peptides (CNP and Ang II) are neuroendocrine hormones acting in concert with changes in peripheral ANP or Ang II with opposite actions.

7. ANP counteracts the thirst-inducing and volume expanding roles of brain Ang II in mammals. During volume reduction, ANP plays a permissive role by being inactive allowing Ang II to restore volume. In hemorrhage the effects of peripheral ANP and Ang II are inversely correlated, but in the brain both ANP and Ang II levels are increased specifically in the hy-pothalamus. However, they may still serve to facilitate the respective roles of peripheral Ang II and ANP.

8. The use of antisense oligonucleotides offers a new approach to selectively inhibit ANP mRNA and thereby reveal the physiological effects of ANP.