Principal Investigator:
Amiram Nir MD

Abstract

The natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are secreted from the heart and act in a hormonal manner. They cause vasodilatation, diuresis and natriuresis. C-type natriuretic (CNP) is a paracrine factor secreted from endothelial cells and cardiac myocytes, acting on neighboring cells. The effect of the natriuretic peptides on cardiac myocytes is investigated.
At the cardiac research laboratory we conduct research projects investigating the direct actions and interactions of the natriuretic peptides, with focus on CNP on cultured cardiomyocytes. In collaboration with researchers from the Hebrew University, we study the effect of CNP on myocyte contraction, in order to understand its mechanism.
The opposing mitogenic effects of the natriuretic peptides and endothelin have led us to study the effects and interactions of these agents on apoptosis. Preliminary data show pro-apoptotic effects of the natriuretic peptides that are opposed by endothelin. We are now studying the mechanism of these effects.
Ongoing studies at the laboratory are aimed at comparing the actions of the different natriuretic peptides (ANP, BNP, CNP, DNP) on cultured cardiac myocytes, as well as further define the effect of these peptides on apoptosis.
Plans for future studies include the definition of the changing role of the natriuretic peptides with maturation, as there seem to be different effects of these peptides on myocytes from neonatal and from adult animals.
Another general future direction for research is the comparison of the effects of the natriuretic peptides and endothelin on myocytes from the left and the right ventricle. Our hypothesis is that the better compliance of the right ventricle is, at least partially, due to a higher natriuretic peptide effect (peptide content, receptor density and/or post-receptoral factors).
Plasma levels of the natriuretic peptides, especially BNP, have been shown to be a very sensitive indicator for cardiac disease. We have conducted a study that assessed plasma BNP levels in children following liver transplantation. Another planned project is measurement of BNP levels in children with rheumatic fever.
In addition we intend to establish assays to measure the natriuretic peptide levels and to provide a neurohumoral profile of patients. This will serve both in the clinical and will improve patient care.

Status:

Laboratory experiments