From Hypertension to Heart Failure: Role of Nitric Oxide–Mediated Endothelial Dysfunction and Emerging Insights from Myocardial Contrast Echocardiography

There is growing evidence that nitric oxide (NO)–mediated endothelial dysfunction occurs in hypertension and may represent the earliest stage of target organ damage, which ultimately leads to hypertensive heart disease and heart failure (HF). An understanding of how impaired myocardial microvascular function and flow reserve relate to early remodeling during the transition to HF in patients with hypertension may lead to new therapeutic insights. The hypertrophied heart, which is a feature of the adverse structural remodeling in hypertensive heart disease, may be accompanied by impaired coronary flow reserve (CFR). Reduced CFR could potentially cause subendocardial ischemia during conditions of high metabolic demand, such as uncontrolled hypertension and tachycardia. Such vulnerability of the subendocardium to abnormal perfusion or ischemia may accelerate the progression from compensated hypertrophy to HF. In this review, we discuss preliminary evidence that altered NO balance may contribute to cardiac hypertrophy–mediated myocardial ischemia. We also describe early results with myocardial contrast echocardiography in the postulated transition from compensated hypertrophy to cardiac failure. These data support further evaluation of NO mediators as potential targets for novel therapies in hypertensive heart disease.