Differences between angiotensin-converting enzyme inhibition and angiotensin II-AT1 antagonism on angiotensin-mediated responses in human internal mammary arteries.
The current study aimed to demonstrate differences between angiotensin (Ang)-converting enzyme (ACE) inhibition and Ang II-AT1 receptor antagonism on full concentration-contraction responses to Ang I. Contraction responses to increasing concentrations of Ang I (1 nM-1 microM) were evaluated in organ baths in the presence of captopril (10 microM-1 mM) with or without a chymase inhibitor (1 microM soybean trypsin inhibitor), or irbesartan (0.1 nM-microM), in internal mammary arteries from 25 patients undergoing coronary bypass surgery. Responses were expressed as a percentage of the control response to 10 microM phenylephrine. Captopril did not change the maximum response to Ang I (control: 46.3 +/- 6.3%, captopril: 43.0 +/- 4.6%). In contrast, 0.1 microM irbesartan completely blocked the maximum response to Ang I (from 45.8 +/- 6.7% to 1.9 +/- 1.9%, p < 0.001). However, addition of soybean trypsin inhibitor to captopril more effectively shifted -log pD2 than captopril alone (0.47 +/- 0.06 vs 0.95 +/- 0.14 log units, p = 0.007). Ang I-mediated effects are much more effectively inhibited by Ang II antagonism than by ACE inhibition. The incomplete effects of captopril on the inhibition of Ang II formation might be caused by alternative Ang II forming enzyme(s), as was demonstrated by the additive effects of soybean trypsin inhibitor added to captopril.
Voors
Adriaan A
AA
Department of Cardiology, Heart Lung Center Utrecht, St. Antonius Hospital, Nieuwegein, The Netherlands. voor02@antonius.net
Oosterga
Margreeth
M
Buikema
Hendrik
H
Mariani
Massimo
M
Grandjean
Jan G
JG
van Gilst
Wiek H
WH
D000368:Aged; D000369:Aged, 80 and over; D000803:Angiotensin I / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A