title: Role of nitric oxide in the progression of cardiovascular remodeling induced by carotid arterio-venous shunt in rabbits.
abstract: Despite a variety of biological roles for nitric oxide (NO) in the cardiovascular system, little is known about whether NO is involved in cardiac hypertrophy. We hypothesized that NO production following a sustained increase in shear stress by volume-overload modifies the level of cardiac hypertrophy independent of hemodynamic changes. Volume-overload was induced by shunt formation between the left common carotid artery and the external jugular vein in 21 rabbits. These shunt rabbits were randomly assigned to 3 groups: shunt with no treatment (n = 8), shunt treated with a low dose of N(G)-nitro-L-arginine methyl ester (L-NAME. 0.5 g/L in drinking water, n=8), and shunt with a high dose of L-NAME (1.5 g/L, n = 5). Eight sham operated rabbits were used as controls. Treatments were started immediately after operation and were continued for 6 weeks. Chronic volume-overload by shunt formation caused left ventricular dilatation and arterial enlargement proximal to the fistula. The relative wall thickness of the left ventricle was decreased, indicating eccentric cardiac hypertrophy. L-NAME elevated mean arterial blood pressure (P < 0.01) and reduced the increment of cardiac output (P < 0.05). L-NAME attenuated ventricular weight (P < 0.01) ventricular cavity dilatation (P < 0.01). and arterial enlargement (P < 0.05). The re-capitulation of atrial natriuretic factor mRNA in the hypertrophied left ventricular myocardium by volume-overload was attenuated with L-NAME. In this model with chronic volume-overload, NO plays a pivotal role in the progression of cardiovascular remodeling by regulating the loading conditions of the heart.
authors.affiliation: First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Shishido
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Itoh
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
mesh_terms: D000818:Animals; D002302:Cardiac Output; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits; D011897:Random Allocation; D016277:Ventricular Function, Left / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester