Endothelial dysfunction in congestive heart failure: ACE inhibition vs. angiotensin II antagonism.
BACKGROUND
Endothelial dysfunction of the vasculature contributes to the elevated peripheral resistance and reduced myocardial perfusion in congestive heart failure (CHF). The present study systematically investigated the effect of angiotensin II (AT(1))- receptor blockade on vascular superoxide (O(2)(-)) production and endothelial dysfunction.


RESULTS
Vasodilator responses and O(2)(-) production were determined in aortic rings from Wistar rats with experimental CHF 10 weeks after extensive myocardial infarction and compared with sham-operated animals (Sham). Rats were either treated with placebo (P), with the AT(1)-receptor antagonist Irbesartan (50 mg kg(-1) day(-1)) or with the ACE inhibitor Trandolapril (0.3 mg kg(-1) day(-1)). In CHF-P, endothelium-dependent, acetylcholine-induced relaxation was significantly attenuated compared with Sham-P. Chronic treatment with Trandolapril or Irbesartan significantly improved endothelium-dependent relaxation. Aortic O(2)(-) formation was markedly increased in CHF, and was not significantly affected by Trandolapril treatment, while it was reduced by Irbesartan. eNOS expression was reduced in CHF and normalised by both treatments.


CONCLUSIONS
Endothelial vasomotor function in CHF rats was normalised by long-term treatment with an ACE inhibitor or an AT(1)-antagonist. Reduced aortic eNOS expression was normalised by both treatments, whereas aortic superoxide formation was only reduced by the AT(1)-antagonist Irbesartan.
Medizinische Klinik der Julius-Maximilians-Universität Würzburg, Josef Schneider Str. 2, D-97080 Würzburg, Germany.
Andreas
A
Schäfer
Daniela
D
Fraccarollo
Piet
P
Tas
Isabel
I
Schmidt
Georg
G
Ertl
Johann
J
Bauersachs
D000704:Analysis of Variance; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy*; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077405:Irbesartan; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007211:Indoles; D013777:Tetrazoles; D013481:Superoxides; C052035:trandolapril; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000077405:Irbesartan