title: Left ventricular hypertrophy induced by aortic banding impairs relaxation of isolated coronary arteries.
abstract: LVH (left ventricular hypertrophy) is associated with impaired coronary vascular reserve. In the present study, we examined the effect of pressure-overload hypertrophy on vasorelaxant responses of guinea-pig isolated coronary small arteries and compared them with mesenteric small arteries. Pressure-overload was induced by banding the ascending aorta of guinea-pigs. Haemodynamics, and ventricular, atrial and lung weights were measured 168 days after banding. Isolated coronary and mesenteric small arteries were contracted with a thromboxane mimetic (U46619) and relaxation to ACH (acetylcholine), ISO (isoprenaline), FSK (forskolin) and SNP (sodium nitroprusside) was examined. Arterial wall morphology was examined by light microscopy. Aortic banding reduced cardiac output and increased systemic vascular resistance; atrial, ventricular and lung weights were increased. Coronary artery adventitial and medial thickness were increased, but mesenteric arterial wall morphology was unaffected. Coronary artery relaxation to ACH, ISO, FSK and SNP were reduced in banded animals. In contrast, relaxation of mesenteric arteries to ACH, FSK and SNP were unaffected by banding, although ISO-induced relaxation was reduced. A COX (cyclo-oxygenase) inhibitor, indomethacin, had no effect on coronary artery responses to ACH in banded or sham animals, but the differences in relaxation of coronary arteries between banded and sham animals were no longer significant following pre-incubation with the NO inhibitors L-NMMA (N(G)-monomethyl-L-arginine) and oxyhaemoglobin. In conclusion, pressure-overload-induced LVH causes impaired relaxation of small coronary arteries to endothelium-dependent and -independent relaxants. These findings are indicative of alterations in vascular smooth muscle responsiveness to vasodilators. Impairment of coronary arterial vasodilation may contribute to the reduced coronary vascular reserve seen in LVH.
authors.affiliation: Clinical Pharmacology, International Centre for Circulatory Health, National Heart and Lung Institute Division, Faculty of Medicine, Imperial College London, St Mary's Hospital, London W2 1NY, UK.
authors.forename: Rory B
authors.initials: RB
authors.lastname: McGoldrick
authors.forename: Martyn
authors.initials: M
authors.lastname: Kingsbury
authors.forename: Mark A
authors.initials: MA
authors.lastname: Turner
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Sheridan
authors.forename: Alun D
authors.initials: AD
authors.lastname: Hughes
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications* / Q000503:physiopathology; D001794:Blood Pressure; D002302:Cardiac Output; D003331:Coronary Vessels / Q000503:physiopathology*; D006168:Guinea Pigs; D006339:Heart Rate; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D014655:Vascular Resistance; D014664:Vasodilation; D014665:Vasodilator Agents
chemical_list: D014665:Vasodilator Agents