Effects of natriuretic peptides on sinoatrial node function and arrhythmogenesis in heart disease

Each and every heart beat is initiated by a natural pacemaker in our hearts called the sinoatrial node. Normal sinoatrial node function is what ensures our heart rate is normal and that the heart is properly able to pump blood to our bodies. Common forms of cardiovascular disease, including hypertension (high blood pressure) and heart failure result in serious damage to the sinoatrial node. This leads to life threatening arrhythmias (irregular heart beats). Although sinoatrial node disease is very common in these conditions very little is known about why this happens our how we can treat it, in part because it is technically very challenging to study the specialized sinoatrial node tissues. Currently, people with sinoatrial node disease have to get an artificial pacemaker, which is costly and has a number of serious limitations. My laboratory is one of only a few worldwide that can routinely study the sinoatrial node in mice (including at the cellular level), which is critical because this enables us to make use of genetically altered mice in our experiments. We have developed a model of sinoatrial node disease (caused by making mice hypertensive) and begun to investigate the effects of a family of hormones called natriuretic peptides on the sinoatrial node in the diseased heart. We have discovered that natriuretic peptides are strong regulators of heart rate and sinoatrial node function in the normal heart. Furthermore, we have found that natriuretic peptides can prevent sinoatrial node disease and arrhythmias in the diseased heart. Natriuretic peptide effects are complex because there are several forms of these hormones and they can cause their effects in a number of different ways. Our proposed experiments will help us understand the complex effects of natriuretic peptides in the diseased heart. Our ultimate goal is to use this information to generate new synthetic natriuretic peptides for the treatment and prevention of heart disease.