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1 Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697; 2 Regulatory Peptide Center, Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68178; and 3 Center for Reproduction of Endangered Species, Zoological Society of San Diego, San Diego, California 92112
The structures and biological activities
of the isoforms of endothelin (ET) in a reptile are unknown. ET-3,
whose primary structure is identical to human ET-3 except for the
substitution Phe4 
Tyr, and a peptide identical to human
ET-1 were isolated from an extract of the lung of the alligator,
Alligator mississipiensis. Bolus intravenous injections of
alligator ET-3 (10, 30, and 100 pmol/kg) into anesthetized alligators
produced dose-dependent decreases in systemic blood pressure
(Psys) and systemic vascular resistance (Rsys)
without change in heart rate (HR), systemic blood flow
(Qsys), pulmonary pressure (Ppul), pulmonary
vascular resistance (Rpul), or pulmonary blood flow
(Qpul). At a dose of 300 pmol/kg, the initial
vasodilatation was followed by an increase in Rsys and
decreases in Qsys and Ppul. The response to
intravenous human/alligator ET-1 (10, 30, 100, and 300 pmol/kg) was
biphasic at all doses with initial decreases in Psys and
Rsys being followed by sustained increases in these
parameters. In the pulmonary circulation, ET-1 produced a
dose-dependent decrease in Qpul and an increase in
Rpul during the first phase of the response but no
significant change during the second phase. There was no change in HR
in response to ET-1. The vasodilatator action of arginine, but not
ET-1, was attenuated by
N
-nitro-L-arginine methyl ester,
indicating that the effect of the peptide is probably not mediated
through increased synthesis of nitric oxide. The data demonstrate that
the structure of the ET isoforms has been strongly conserved during the
evolution of vertebrates but that cardiovascular actions differ
significantly between the alligator and mammals, especially in the
magnitude and duration of the hypotensive response.
reptile; vasoconstrictor; vasodilatator; pulmonary; systemic
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