(Circulation. 2000;101:1854.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Impaired Endothelium-Dependent Regulation of Ventricular Relaxation in Pressure-Overload Cardiac Hypertrophy
From the Department of Cardiology, University of Wales College of Medicine, Cardiff (P.A.M.), and GKT School of Medicine, King’s College, London (A.M.S.), UK.
Correspondence to Professor Ajay M. Shah, Department of Cardiology, GKT School of Medicine, King’s College London, Bessemer Rd, London SE5 9PJ, UK. E-mail ajay.shah{at}kcl.ac.uk
Background—Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation and may benefit diastolic function. Left ventricular hypertrophy (LVH) is characterized by abnormal myocardial relaxation and endothelial dysfunction. We investigated endothelium-dependent regulation of LV relaxation in moderate pressure-overload LVH induced by aortic banding in guinea pigs.
Methods and Results—Isolated ejecting hearts of banded or sham-operated animals (shams) were studied. The specific agonists for endothelial release of NO, bradykinin (10 nmol/L), and substance P (100 nmol/L) both induced earlier onset of LV relaxation in shams (time to LV dP/dtmin [tdP/dtmin], -13.4±3.0 and -10.4±2.5 ms, respectively) without altering peak LV pressure or LV dP/dtmax. Neither agent altered tdP/dtmin in banded animals. The ACE inhibitor captopril (1 µmol/L) also selectively reduced tdP/dtmin in shams via a bradykinin/NO-dependent mechanism but had no effect in banded animals. An exogenous NO donor, sodium nitroprusside (0.1 µmol/L), selectively reduced tdP/dtmin to a similar extent in both shams and banded animals. Endothelial-type NO synthase (eNOS) protein expression in whole LV homogenate was unaltered in banded animals.
Conclusions—Endothelium-dependent enhancement of LV relaxation is impaired in moderate pressure-overload LVH, despite a preserved response to exogenous NO. This is not accounted for by altered eNOS expression. These abnormalities may contribute to diastolic dysfunction in LVH.
Key Words: nitric oxide • diastole • hypertrophy • endothelium
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