Acetylcholine stimulated dilatation and stretch induced myogenic constriction in mesenteric artery of rats with chronic heart failure.
Rats with chronic heart failure (CHF) develop increased myogenic constriction in mesenteric resistance arteries. Here we investigated increased myogenic constriction in relation to alterations in EDHF- and NO-mediated dilatation in CHF-rats. Male Spraque-Dawley rats were subjected to myocardial-infarction or sham-surgery. At 9-10 weeks after surgery, isolated mesenteric artery ring preparations were studied in a wire-myograph. Stretch-induced myogenic constriction was obtained by stepwise increase of the internal circumference diameter (0.5-1.2 L100). Cyclooxygenase- and eNOS-inhibitors were employed to study NO- and EDHF-mediated dilatation in response to acetylcholine. Rats with CHF (n=8), but not sham-rats (n=6), developed significant myogenic constriction. In addition, the contribution of endothelial dilator mediators was significantly altered in CHF-rats, with increased dependency on NO and decreased EDHF-mediated dilatation. Moreover, EDHF-mediated dilatation was inversely correlated with myogenic constriction in individual CHF-rats (r=-0.74, p=0.04). These data demonstrate increased myogenic constriction in mesenteric arteries of rats with CHF post-MI to be correlated to decreased EDHF-mediated dilatation. These findings extend the previous observation that myogenic constriction antagonizes EDHF-mediated dilatation in rat coronary artery under normal conditions, and suggests this relationship also to become functional in mesenteric arteries under pathophysiological conditions of CHF.
Xu
Y
Y
Groningen University Institute for Drug Exploration, Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, A.Deusinglaan 1, 9713 AV Groningen, The Netherlands. y.xu@med.umcg.nl
Henning
R H
RH
Lipsic
E
E
van Buiten
A
A
van Gilst
W H
WH
Buikema
H
H
D000109:Acetylcholine; D000818:Animals; D001685:Biological Factors; D004727:Endothelium / Q000187:drug effects; D006333:Heart Failure / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D023421:Models, Animal; D009203:Myocardial Infarction; D051381:Rats; D017207:Rats, Sprague-Dawley
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D000109:Acetylcholine