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CHRONIC DECREASE IN FLOW CONTRIBUTES TO HEART FAILURE‐INDUCED ENDOTHELIAL DYSFUNCTION IN RATS
Author(s) -
Devaux C,
Iglarz M,
Richard V,
Mulder P,
Henrion D,
Renet S,
Henry JP,
Thuillez C
Publication year - 2004
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2004.03997.x
Subject(s) - medicine , enos , heart failure , vasodilation , endothelial dysfunction , blood flow , endocrinology , nitric oxide , endothelium , artery , cardiology , ligation , hemodynamics , nitric oxide synthase
Summary 1. 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. 2. 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. 3. Chronic heart failure induced a decrease in mesenteric blood flow (374 ± 25 and 305 ± 27 µL/min for sham and CHF, respectively; P < 0.05). Neither CHF nor the chronic increase in flow affected the responses to acetylcholine. 4. 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). 5. 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. 6. A chronic increase in flow significantly increased the abundance of eNOS mRNA in sham rats, but only moderately and non‐significantly in CHF rats. 7. Thus, endothelial dysfunction of small arteries in CHF appears to be largely the consequence of the chronic decrease in flow.