Kinase II-dependent formation of angiotensins II and III in the hepatic circulation.
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)
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000097:blood; D000805:Angiotensin III / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D005260:Female; D007700:Kinetics; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*
D000804:Angiotensin II; D000805:Angiotensin III; C014623:angiotensin III, Ile(8)-; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D009638:Norepinephrine