Angiotensin-converting enzyme inhibition modifies angiotensin but not kinin peptide levels in human atrial tissue.
Angiotensin-converting enzyme (ACE) converts angiotensin I (Ang I) to angiotensin II (Ang II) and metabolizes bradykinin and kallidin peptides. Decreased Ang II levels and increased kinin peptide levels are implicated in the mediation of the therapeutic effects of ACE inhibition. However, alternative non-ACE pathways of Ang II formation have been proposed to predominate in human heart. We investigated the effects of ACE inhibition on cardiac tissue levels of angiotensin and kinin peptides. High-performance liquid chromatography-based radioimmunoassays were used to measure angiotensin peptides and hydroxylated and nonhydroxylated bradykinin and kallidin peptides in right atrial appendages of subjects who had been prepared for cardiopulmonary bypass. Peptide levels in subjects who received ACE inhibitor therapy were compared with those who did not receive ACE inhibitor therapy. ACE inhibition reduced Ang II levels, which was associated with an 80% reduction in the Ang II/Ang I ratio. ACE inhibition did not modify either bradykinin or kallidin peptide levels or the bradykinin-(1-7)/bradykinin-(1-9) ratio. The 80% reduction in the Ang II/Ang I ratio by ACE inhibition indicated a primary role for ACE in the conversion of Ang I to Ang II in atrial tissue. These data support a role for reduced Ang II levels but do not support a role for increased kinin peptide levels in mediating the direct cardiac effects of ACE inhibition.
Campbell
D J
DJ
St Vincent's Institute of Medical Research, Victoria, Australia. j.campbell@medicine.unimelb.edu.au
Duncan
A M
AM
Kladis
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000803:Angiotensin I / Q000032:analysis; D000804:Angiotensin II / Q000032:analysis*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001920:Bradykinin / Q000032:analysis / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D005260:Female; D006325:Heart Atria / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007609:Kallidin / Q000032:analysis / Q000378:metabolism; D007705:Kinins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000032:analysis; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011863:Radioimmunoassay
D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D010455:Peptides; D000804:Angiotensin II; D007609:Kallidin; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin