Dr. Mercedes L. Kuroski deBold
The role of the heart in fluid volume and blood pressure regulation was expanded rapidly by the discovery of hormones that are produced by the heart. These hormones are referred to as natriuretic peptides (NP). Natriuretic peptides are capable of profoundly affecting the function of blood vessels, the kidneys as well as several other systems of cardiovascular importance. Following the discovery of atrial natriuretic factor (ANF) by our group, a second hormone was isolated and called brain natriuretic peptide (BNP). BNP and ANF appear to function in concert in order to regulate salt and water excretion and blood pressure. Elevated ANF and BNP plasma levels as well as increased ANF and BNP gene expression are known to occur in several pathophysiological conditions associated with hemodynamic overload as seen in several hypertensive states. A dymorphic pattern of blood pressure have been reported to occur in several forms of hypertension e.g. the incidence of essential hypertension is lower in premenopausal women than in age matched men. The possible role for ANF in blood pressure control associated with sex is hinted at by the finding that, plasma ANF levels are two fold higher in young women (25-35 yr) than in young men (25-43 yr). The molecular basis for this difference in NP is not known. Our investigations are aimed at elucidating the role of natriuretic peptides ANF and BNP during the development of hypertension and cardiac hypertrophy in male and female rats. Results indicate that there are significant sex differences in the response of the endocrine heart in evolving hypertension. In collaboration with members of the Cardiac Cell and Molecular Biology Group, we have shown that:
ANF contributes to the mineralocorticoid escape phenomenon.
ANF and BNP played a unique role during the development of cardiac hypertrophy in DOCA-salt rats.
Cardiac mesothelial cells synthesize and release endothelin, a factor with mitogenic and vasoconstricting properties. This observation suggest that endothelin might play an important role in the process of determination of adult cardiocyte phenotype.
The immunocytochemical distribution of the natriuretic peptides in the kidneys and the conducting system of the mammalian heart are being investigated.