The effects of C-type natriuretic peptide and its receptors on sinoatrial node function, heart rate regulation and arrhythmogenesis

Natriuretic peptides are a family of related hormones produced in the heart that are very important in the context of normal heart function and heart disease. Heart rate (the number of times the heart beats per minute) regulates the delivery of blood to all regions of the body and is determined by specialized 'pacemaker' cells in a region of the heart called the sinoatrial node. My lab is interested in how natriuretic peptides regulate the specialized sinoatrial node region of the heart. Since we began studying this topic we have found that one kind of natriuretic peptide, called CNP, can potently reduce heart rate by binding to a specific receptor called the natriuretic peptide C receptor (or NPR-C). Originally, scientists thought this NPR-C receptor had no function, but our work is helping to change this idea. Many more experiments are necessary to understand how CNP and the NPR-C receptor affect heart rate and the sinoatrial node. CNP also binds to a second kind of receptor called NPR-B. Very little is known about the role of the NPR-B receptor in the sinoatrial node; therefore, we are also studying this receptor so that we may ultimately understand how both NPR-C and NPR-B contribute to heart rate regulation by CNP. This work is important because heart failure is characterized by the occurrence of life threatening arrhythmias, some of which are associated with dysfunction of the sinoatrial node. The body increases its production of natriuretic peptides in heart disease because these peptides help prevent heart failure from worsening over time. We hypothesize that natriuretic peptides will be effective in treating or preventing arrhythmias during heart failure in people and believe our work will help lead to significant improvements in the use and development of synthetic natriuretic peptides for the treatment of people suffering from heart failure, arrhythmias and other forms of heart disease.