Different effects of angiotensin-converting enzyme inhibition in human arteries and veins.
The renin-angiotensin system (RAS) participates in the regulation of vascular tone; its effects were studied in human internal mammary artery (IMA) and saphenous vein (SV) suspended in organ chambers for isometric tension recording. The angiotensin-converting enzyme (ACE) inhibitor enalaprilat (10(-7) M) markedly augmented endothelium-dependent relaxations to bradykinin in SV (concentration shift: 10-fold; n = 6; p < 0.005), but not in IMA; in both blood vessels, it had no effect on endothelium-dependent relaxations to acetylcholine. The contractions to angiotensin I (Ang I; 10(-7) M) were markedly inhibited by enalaprilat (10(-7) M) in SV (control: 34 +/- 6% of 100 mM KCl; treatment: 18 +/- 6%; n = 7; p < 0.05) but not in IMA (control: 33 +/- 4%; treatment: 30 +/- 6%; n = 7; NS) and abolished by the Ang II receptor antagonist DuP 753 (10(-7) M) in both blood vessels. Ang II (10(-7) M) induced more pronounced contractions than Ang I in IMA (63 +/- 4%) and SV (63 +/- 5%; n = 5-6; p < 0.05 vs. Ang I), which was markedly inhibited by DuP 753 (10(-7) M; IMA: 21 +/- 5%; SV: 32 +/- 5%; p < 0.05). Thus, in SV but not IMA, ACE inactivates bradykinin and thereby blunts endothelium-dependent relaxations to the peptide and converts Ang I to Ang II.
Yang
Z
Z
Department of Medicine, University Hospitals Basel, Switzerland.
Arnet
U
U
von Segesser
L
L
Siebenmann
R
R
Turina
M
M
Lüscher
T F
TF
D000109:Acetylcholine / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D000803:Angiotensin I; D015773:Enalaprilat; D019808:Losartan; D000109:Acetylcholine; D001920:Bradykinin; D009638:Norepinephrine