Effects of ramipril on endothelial function and the expression of proinflammatory cytokines and adhesion molecules in young normotensive subjects with successfully repaired coarctation of aorta: a randomized cross-over study.
OBJECTIVE
The purpose of this study was to evaluate the effect of ramipril on endothelial function and inflammatory process in a group of normotensive subjects with successfully repaired coarctation of the aorta (SCR).


BACKGROUND
Subjects with SCR experience higher long-term cardiovascular risk as a result of the relapse of arterial hypertension or owing to nonreversible structural changes in the pre-coarctation arterial tree. These subjects experience endothelial dysfunction in the right forearm and appear to have elevated levels of proatherogenic inflammatory markers, even in the absence of arterial hypertension.


METHODS
Twenty young individuals age 27.3 +/- 2.4 years old with SCR 13.9 +/- 2.2 years previously, received ramipril 5 mg/day for 4 weeks in a randomized, cross-over, controlled trial. Endothelial function was evaluated in the right forearm by gauge-strain plethysmography, and serum levels of interleukin (IL)-1b, IL-6, soluble CD40 ligand (sCD40L), and soluble vascular cell adhesion molecule (sVCAM)-1 were determined by enzyme-linked immunosorbent assay.


RESULTS
Ramipril improved endothelial function (p < 0.001) and decreased the expression of proinflammatory cytokine IL-6 (p < 0.05) and sCD40L (p < 0.01). Furthermore, ramipril decreased serum levels of sVCAM-1 (p < 0.01) but failed to affect serum levels of C-reactive protein. These effects were independent of blood pressure lowering.


CONCLUSIONS
Ramipril reversed the impaired endothelial function and decreased the expression of proinflammatory cytokine IL-6, sCD40L, and adhesion molecules in normotensive subjects with SCR. These findings imply that ramipril treatment may have antiatherogenic effects in subjects with SCR, even in the absence of arterial hypertension.
Brili
Stella
S
First Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece.
Tousoulis
Dimitris
D
Antoniades
Charalambos
C
Vasiliadou
Carmen
C
Karali
Maria
M
Papageorgiou
Nikos
N
Ioakeimidis
Nikos
N
Marinou
Kyriakoula
K
Stefanadi
Elli
E
Stefanadis
Christodoulos
C
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001017:Aortic Coarctation / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D002097:C-Reactive Protein / Q000032:analysis; D023201:CD40 Ligand / Q000097:blood; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D010991:Plethysmography; D017257:Ramipril / Q000494:pharmacology*; D012039:Regional Blood Flow; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D053583:Interleukin-1beta; D019010:Vascular Cell Adhesion Molecule-1; D023201:CD40 Ligand; D002097:C-Reactive Protein; D017257:Ramipril