Understanding Nitric Oxide Physiology in the Heart: A Nanomedical Approach

Nitric oxide (NO) is a ubiquitous signaling molecule synthesized from l-arginine and oxygen. The process is catalyzed by NO synthase (NOS), an enzyme expressed in both constitutive (endothelial, neuronal) and inducible forms. Uncoupling of constitutive NOS leads to overproduction of superoxide (O2−) and peroxynitrite (ONOO−), 2 potent oxidants. Nanosensing techniques have been developed to monitor the physiology of NO in the beating heart in vivo. These methods involve the application of nanosensors to monitor real-time dynamics of NO production in the heart as well as the dynamics of oxidative species (oxidative stress) produced in the failing heart. Results of a recent study using nanotechnology demonstrated that African Americans have an inherent imbalance of NO, O2−, and ONOO− production in the endothelium. The overproduction of O2− and ONOO− triggers the release of aggressive radicals and damages cardiac muscle (necrosis), which may explain why African Americans are at greater risk for developing cardiovascular diseases, such as hypertension and heart failure, and are more likely to have complications than European Americans. Potential therapeutic strategies to prevent or ameliorate damage to the heart during cardiac events are prevention of O2− and ONOO− production, supplementation of NO (NO donors), and scavenging of O2− (antioxidants).