Synthesis of nonmammalian angiotensins and their comparative pressor properties in dogfish shark, domestic chicken, and rat.

To understand how vertebrates utilize angiotensins during evolutionary development, we undertook studies to synthesize and/or characterize angiotensin-like peptides from nonmammalian species. The present paper describes the synthesis of [Asp1,Val5,Asn9] angiotensin I (bull frog, Rana catesbeiana) (I), [Asn1,Val5,His9] angiotensin I (Japanese goosefish, Lophius litulon) (II), [Asn1, Val5,Asn9] angiotensin I (chum salmon, Oncorhynchus keta) (III), and [Asn1, Val5,Tyr9] angiotensin I (related to native angiotensin in snake, Elaphe climocophora (IV). Pressor properties of these peptides were compared with the peptides isolated from other species and related synthetic analogs in one representative species from three distinct classes of vertebrates: 1) elasmobranchs: spiny dogfish shark; 2) birds: domestic chicken; and 3) mammals: rat. The effect of angiotensins on short circuit current (to compare sodium and water permeability) was studied by adding these on the dermal side of the isolated frog skin. In the rat pressor bioassays, the above peptides possessed, respectively, I, 87.8%; II, 51.5%; III, 65.2%; and IV, 60.3% pressor activity of [Ile5] angiotensin II, which was blocked with a converting-enzyme inhibitor, captopril. In the conscious dogfish shark, the percentage increase of blood pressure based on preinjection level (= 100) in the dorsal aortic pressure was 35% to 60% for [Asp1,Ile5,His9] angiotensin I (human) (3 micrograms/kg), [Asp1,Val5,Ser9] angiotensin I (chicken) (3 micrograms/kg), [Asp1,Ile5] angiotensin II (3.6 micrograms/kg), and [Asn1,Val5] angiotensin II (6 micrograms/kg). Likewise, a 30% to 35% increase in blood pressure was obtained with angiotensin III (3 micrograms/kg), [Ile8] angiotensin II (4.4 micrograms/kg), and [Sar1,Ile8] angiotensin II (9.1 micrograms/kg). [Sar1,Thr8] angiotensin II and [Ile8] angiotensin I did not produce a significant pressor response even at high dose-level (8 micrograms/kg).(ABSTRACT TRUNCATED AT 250 WORDS)