title: Acetylcholine stimulated dilatation and stretch induced myogenic constriction in mesenteric artery of rats with chronic heart failure.
abstract: 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.
authors.affiliation: 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
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: R H
authors.initials: RH
authors.lastname: Henning
authors.forename: E
authors.initials: E
authors.lastname: Lipsic
authors.forename: A
authors.initials: A
authors.lastname: van Buiten
authors.forename: W H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: H
authors.initials: H
authors.lastname: Buikema
mesh_terms: 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
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D000109:Acetylcholine