title: Chronic decrease in flow contributes to heart failure-induced endothelial dysfunction in rats.
abstract: Chronic heart failure (CHF) impairs endothelium-dependent, nitric oxide (NO)-mediated dilation. This decreased dilation may be partly secondary to the chronic decrease in blood flow, but this hypothesis has not yet been tested. Thus, we assessed whether a localized, chronic increase in blood flow in vivo reverses endothelial dysfunction of small arteries in rats with CHF. Two months after coronary artery ligation or sham surgery, second-order side branches of the superior mesenteric artery were ligated in order to obtain persistently elevated blood flow (HF) in the adjacent first-order side branch compared with normal vessels (NF). One month later, responses to acetylcholine and flow-mediated vasodilatation (FMD) were assessed in vitro in an arteriograph. Chronic heart failure induced a decrease in mesenteric blood flow (374 +/- 25 and 305 +/- 27 micro L/min for sham and CHF, respectively; P < 0.05). Neither CHF nor the chronic increase in flow affected the responses to acetylcholine. Chronic heart failure decreased FMD (maximal response in sham and control 34 +/- 6 and 13 +/- 4%, respectively; P < 0.05). Chronic increases in blood flow did not modify FMD in sham, but restored FMD in CHF rats (28 +/- 4%; P < 0.05 vs CHF NF). The restored response was abolished by an inhibitor of NO synthesis (N(G)-nitro-l-arginine). Chronic heart failure did not affect the abundance of mesenteric endothelial NO synthase (eNOS) mRNA. A chronic increase in flow significantly increased the abundance of eNOS mRNA in sham rats, but only moderately and non-significantly in CHF rats. Thus, endothelial dysfunction of small arteries in CHF appears to be largely the consequence of the chronic decrease in flow.
authors.affiliation: INSERM U644, IFRMP 23, Rouen, France.
authors.forename: C
authors.initials: C
authors.lastname: Devaux
authors.forename: M
authors.initials: M
authors.lastname: Iglarz
authors.forename: V
authors.initials: V
authors.lastname: Richard
authors.forename: P
authors.initials: P
authors.lastname: Mulder
authors.forename: D
authors.initials: D
authors.lastname: Henrion
authors.forename: S
authors.initials: S
authors.lastname: Renet
authors.forename: J P
authors.initials: JP
authors.lastname: Henry
authors.forename: C
authors.initials: C
authors.lastname: Thuillez
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D051381:Rats; D013152:Splanchnic Circulation / Q000502:physiology*; D014652:Vascular Diseases / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000109:Acetylcholine