title: Volume overload left ventricular hypertrophy: effects on coronary microvascular reactivity in rabbits.
abstract: The mechanisms controlling the coronary vascular responses of vessels perfusing the left ventricular (LV) myocardium that is hypertrophied from chronic volume overload are unclear. We hypothesised that endothelial function is compromised, and receptor-mediated contraction is exacerbated, in coronary resistance vessels from rabbits with LV hypertrophy compared to controls. The mitral valve of 10 rabbits was damaged surgically to cause mitral regurgitation and chronic volume overload, resulting in LV hypertrophy (LV hypertrophy rabbits). Echocardiographic assessment at 12 weeks verified that mitral regurgitation was present in LV hypertrophy but not sham-operated, weight- and age-matched animals (control rabbits; n = 17). Percentage increases from weeks 0 to 12 in LV cross-sectional area (47 +/- 7 % vs. 2 +/- 8 %), LV volume (47 +/- 14 % vs. 7 +/- 10 %) and LV mass (27 +/- 4 % vs. 3 +/- 6 %), were greater (all P < 0.05) in LV hypertrophy vs. control rabbits, respectively. At 12 weeks, coronary resistance vessel (approximately 130 microm, internal diameter) reactivity was evaluated using wire myography. Endothelium-dependent (i.e. acetylcholine, 10(-8)-10(-5) M) and -independent (i.e. sodium nitroprusside, 10(-9)-10(-4) M) relaxation, and receptor-mediated vasocontraction (i.e. endothelin-1, 10(-11)-10(-7) M) were similar between groups. However, tension development in response to nitric oxide synthase inhibition (10(-6) M N (G)-monomethyl-L-arginine) was greater (P < 0.05) in LV hypertrophy compared to control rabbits. These results indicate that while coronary resistance vessel function is similar between groups, our estimate of basal nitric oxide production is greater in vessels from LV hypertrophy than control rabbits.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, TB 172, One Shields Avenue, Davis, CA 95616, USA. j.david.symons@hsc.utah.edu
authors.forename: J D
authors.initials: JD
authors.lastname: Symons
authors.forename: S
authors.initials: S
authors.lastname: Gunawardena
authors.forename: C T
authors.initials: CT
authors.lastname: Kappagoda
authors.forename: M R
authors.initials: MR
authors.lastname: Dhond
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology; D002908:Chronic Disease; D003326:Coronary Circulation / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology; D006940:Hyperemia / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008944:Mitral Valve Insufficiency / Q000473:pathology / Q000503:physiopathology; D009200:Myocardial Contraction; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D012016:Reference Values; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left
chemical_list: D019332:Endothelin-1; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000109:Acetylcholine