Synthesis and pharmacology of nonmammalian angiotensins and their evolutionary development

To understand how vertebrates utilize angiotensins during evolutionary development studies were undertaken to synthesize and/or characterize angiotensin-like peptides from nonmammalian species. These studies indicated the presence of a new L-asparaginase amidohydrolase type enzyme in eel plasma which deamidates L-asparagine residue at the amino terminus of the angiotensin peptides, thereby implying that l-asparaginyl decapeptide (rather than l-aspartyl decapeptide) is the natural form of angiotensin inherent in eel plasma. Pharmacological properties of the nonmammalian angiotensins compared with the synthetic analogs in one representative species of three distinct classes of vertebrates suggest that: in spite of variation in position 9 of the nonmammalian angiotensins I, the pressor activity of these peptides in rat and in dogfish shark is due to their conversion into the corresponding angiotensin II; in relatively more primitive stages of evolution, when vertebrates lived in salt water (e.g., dogfish shark) pressor action of exogenous angiotensin II appears to be due to the release of catecholamines (and not through direct vasoconstrictor effects, as in the mammalian species); and frog-skin angiotensin II has properties that may prove to be compatible with a role in the regulation of salt and water in amphibians.