title: Inhibition of angiotensin-converting enzyme and phosphodiesterase type 5 improves endothelial function in heart failure.
abstract: ACE (angiotensin-converting enzyme) inhibitors and PDE5 (phosphodiesterase type 5) inhibitors have each been reported to improve endothelial function in cardiovascular disease patients, but the comparative and combined effects of these two classes have not been studied previously. We sought to characterize the acute effects of ramipril alone, sildenafil alone, or their combination on endothelial function in patients with CHF (chronic heart failure). CHF subjects (n=64) were randomized to receive placebo, 10 mg of ramipril alone, 50 mg of sildenafil alone or a combination of ramipril and sildenafil in a double-blind manner. FMD (flow-mediated dilation) of the brachial artery was determined by high-resolution ultrasound imaging before and at 1, 2 and 4 h after administration of the study drug. Ramipril alone increased FMD at 4 h compared with placebo (+2.3+/-1.3%, P=0.02). Sildenafil alone increased FMD at 1, 2 and 4 h compared with placebo (+3.9+/-1.4, +4.6+/-1.8 and +3.7+/-1.3% respectively, all P<0.02). Sildenafil in combination with ramipril increased FMD at 1, 2 and 4 h when compared with placebo (+3.5+/-1.5, +4.5+/-1.8 and +4.8+/-1.3% respectively, all P<0.03). Ramipril and sildenafil both acutely improved FMD in patients with CHF, with additive effects evident at 4 h during combination therapy. Therefore further work to characterize chronic effects of combined ACE and PDE5 inhibition on endothelial function are warranted.
authors.affiliation: Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT 06510, U.S.A.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Hryniewicz
authors.forename: Clarito
authors.initials: C
authors.lastname: Dimayuga
authors.forename: Alhakam
authors.initials: A
authors.lastname: Hudaihed
authors.forename: Ana Silvia
authors.initials: AS
authors.lastname: Androne
authors.forename: Haoyi
authors.initials: H
authors.lastname: Zheng
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jankowski
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Katz
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000502:physiology*; D010879:Piperazines / Q000627:therapeutic use; D011446:Prospective Studies; D011687:Purines; D017257:Ramipril / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones; D014463:Ultrasonography
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D020097:Natriuretic Peptide, Brain; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D017257:Ramipril; D009638:Norepinephrine