Peripheral artery structure and endothelial function in heart failure: effect of ACE inhibition.
Chronic heart failure (CHF) induces peripheral vasoconstriction and impairs endothelium-dependent relaxation of large arteries. We investigated in a rat model of CHF (coronary artery ligation) 1) whether endothelial dysfunction also exists in resistance arteries, 2) whether this is associated with vascular morphological changes, and 3) the effect of angiotensin-converting enzyme (ACE) inhibition on these parameters. After 1 mo or 1 yr, CHF reduced the vasodilatory response to acetylcholine of isolated, perfused femoral and mesenteric artery segments. This impairment was more marked in femoral than in mesenteric arteries. However, CHF did not induce any arterial remodeling. Chronic treatment with the ACE inhibitor perindopril improved the response to acetylcholine and reduced media cross-sectional area and collagen density. Thus at the level of small peripheral arteries, CHF induces an endothelial dysfunction but does not affect vascular structure. ACE inhibition prevents the CHF-induced endothelial dysfunction and induces vascular remodeling. These changes could contribute to the observed beneficial effects of ACE inhibitors on hemodynamics and survival in CHF.
Mulder
P
P
Department of Pharmacology, Rouen University Medical School, France.
Elfertak
L
L
Richard
V
V
Compagnon
P
P
Devaux
B
B
Henry
J P
JP
Scalbert
E
E
Desché
P
P
Macé
B
B
ThuilleZ
C
C
D000109:Acetylcholine / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002303:Cardiac Output, Low / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005263:Femoral Artery / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology; D009599:Nitroprusside / Q000494:pharmacology; D020913:Perindopril; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D000803:Angiotensin I; D000109:Acetylcholine; D020913:Perindopril