Enzymatic formation of angiotensins II and III in the hindlimb circulation of dogs.
Experiments were performed in 14 anesthetized dogs to (1) to determine if the reductions in hindlimb blood flow produced by [des-Asp1] angiotensin I were due to its local enzymatic (kininase II) conversion to angiotensin III and (2) to quantitate the extent of conversion of angiotensin I to angiotensin II and of [des-Asp1] angiotensin I to angiotensin III in the hindlimb circulation. Graded doses of these peptides were administered as bolus injections directly into the left external iliac artery while measuring flow in this artery electromagnetically. Dose-response relationships were determined before and during the inhibition of kininase II activity with captopril or antagonism of angiotensin receptor sites with [Ile7] angiotensin III. Captopril inhibited the vasoconstrictor responses to angiotensin I and [des-Asp1] angiotensin I, but did not affect the responses to angiotensins II or III, or norepinephrine. [Ile7] angiotensin III inhibited the vasoconstrictor responses to all four angiotensin peptides but did not alter the responses to norepinephrine. These findings indicate that the hindlimb vasoconstrictor responses to [des-Asp1] angiotensin I were due to the local formation of angiotensin III. The extent of conversion of [des-Asp1] angiotensin I to angiotensin III that occurred in one transit through the hindlimb arterial circulation was estimated to be 36.7%, which was not different from the estimated 36.4% conversion of angiotensin I to angiotensin II. We conclude that angiotensin I and [des-Asp1] angiotensin I are converted to their respective vasoactive forms (angiotensins II and III) to a similar extent in the hindlimb circulation via the action of kininase II.
D000803:Angiotensin I / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology; D000805:Angiotensin III / Q000097:blood* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D007083:Iliac Artery; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D014661:Vasoconstriction / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000805:Angiotensin III; C011437:angiotensin I, des-Asp(1)-; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D004837:Epinephrine