Beneficial effects of quinaprilat on coronary vasomotor function, endothelial oxidative stress, and endothelin activation after human heart transplantation.
BACKGROUND
We evaluated the potential of angiotensin-converting enzyme inhibition (ACEI) to modulate resting coronary vasomotor tone and endothelial dysfunction, and to decrease vascular oxidative stress and endothelin (ET)-1 activity in human heart transplant recipients.


METHODS
Coronary vasomotor responses and transcardiac metabolism of glutathione, oxidized glutathione, and ET-1 were determined before and after quinaprilat infusion in 32 heart transplant recipients. Furthermore, the potential effects of ACEI on endothelial oxidative stress, ET-1 activity, and nitrosoglutathione formation were investigated using endothelial cell cultures.


RESULTS
Epicardial diameter increased in response to quinaprilat by 6% +/- 1% (proximal segments; P<0.05) and 14% +/- 3% (distal segments; P<0.01). Coronary flow velocity increased by 2.2 +/- 0.2 (P<0.03). Coronary vasodilation to quinaprilat was negatively correlated with preexisting functional and structural coronary alterations. Quinaprilat selectively improved epicardial vasomotor response in segments with endothelial dysfunction, whereas microvascular endothelial dysfunction was unchanged. Transcardiac glutathione and big ET levels decreased after quinaprilat, whereas oxidized glutathione and ET-1 concentrations remained unchanged. Cell culture studies showed antioxidative effects of quinaprilat, revealed concentration-dependent down-regulation of endothelial ET-1 release, and indicated formation of nitrosoglutathione by quinaprilat. CONCLUSION.: ACE regulates resting coronary vasomotor tone. Quinaprilat reduces vascular oxidative stress and ET-1 activity and mediates formation of nitrosoglutathione, effects that might contribute to long-term vasculoprotective effects of ACEI after heart transplantation.
Steinhauff
Silke
S
Division of Cardiology, University Hospital Munich-Grosshadern, 81377 Munich, Germany.
Pehlivanli
Sinan
S
Bakovic-Alt
Renata
R
Meiser
Bruno M
BM
Becker
Bernhard F
BF
von Scheidt
Wolfgang
W
Weis
Michael
M
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D019332:Endothelin-1 / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005500:Follow-Up Studies; D016027:Heart Transplantation; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D013997:Time Factors; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D019332:Endothelin-1; D044005:Tetrahydroisoquinolines; C054501:quinaprilat