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PubMed · 15191402

Chronic decrease in flow contributes to heart failure-induced endothelial dysfunction in rats.

C Devaux·M Iglarz·V Richard·P Mulder·D Henrion·S Renet·J P Henry·C Thuillez
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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.

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AcetylcholineAnimalsBlood Flow VelocityChronic DiseaseDose-Response Relationship, DrugEndothelium, VascularHeart FailureRatsSplanchnic CirculationVascular DiseasesVasodilationComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

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C Devaux, M Iglarz, V Richard, P Mulder, D Henrion, S Renet, J P Henry, C Thuillez. Chronic decrease in flow contributes to heart failure-induced endothelial dysfunction in rats.. https://doi.org/10.1111/j.1440-1681.2004.03997.x

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