AJP - Heart and Circulatory Physiology, Vol 245, Issue 5 849-H854, Copyright © 1983 by American Physiological Society
Kinase II-dependent formation of angiotensins II and III in the hepatic circulation
S. L. Britton, G. Thomas, C. Daniel and T. F. Ronau
Experiments were performed in 14 pentobarbital-anesthetized dogs to 1)
determine if the hepatic arterial vasoconstrictor effects of
[des-Asp1]angiotensin I [( des-Asp1]ANG I) were due to its local conversion
to angiotensin III (ANG III) and 2) to evaluate the magnitude of conversion
of ANG I to angiotensin II (ANG II) and of [des-Asp1]ANG I to ANG III in
the hepatic arterial vascular bed. Graded doses of these peptide agonists
were administered as bolus injections directly into the hepatic artery;
hepatic arterial blood flow was measured with an electromagnetic flow
probe. Dose-response relationships were determined before and during the
inhibition of kinase II activity with captopril
(2-D-methyl-3-mercaptopropanoyl-L-proline) and antagonism of angiotensin
receptor sites with [Ile7]angiotensin III [( Ile7]ANG III). ANG I and
[des-Asp1]ANG I were equipotent at all doses tested, as were ANG II and
III. At all doses tested, ANG II and III were approximately three times
more potent than ANG I and [des-Asp1]-ANG I. Captopril attenuated the
vasoconstrictor responses to ANG I and [des-Asp1]ANG I only, whereas
[Ile7]ANG III inhibited the responses to all four angiotensin peptides.
These data indicate that the hepatic arterial vasoconstrictor responses to
[des-Asp1]ANG I were due to the intrahepatic formation of ANG III. The
extent of intrahepatic conversion of [des-Asp1]-ANG I to ANG III that
occurred in one transit through the hepatic arterial vascular bed was
estimated to be 33%, which was similar to the estimated 38% conversion of
ANG I to ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)
