Cardiovascular and renal functions are geared towards the maintenance of the internal environment in the mammalian organism, including the homeostatic regulation of plasma volume and composition, and of blood pressure. Our research has been directed at some of the hormones and receptors involved in these essential homeostatic mechanisms. Particular attention has been devoted in the past decade to the study of atrial natriuretic factor (ANF) and its receptors.

Studies by several laboratories, including our own, revealed that ANF is a 28 amino acid polypeptide hormone secreted by the heart atria when blood volume or pressure increases. ANF leads to an increase in sodium excretion by the kidney, an inhibition of the renin-angiotensin-aldosterone system, vasorelaxation, and an increase in capillary permeability that tend to return plasma volume and pressure to normal levels. These effects are mediated by a specific receptor (GCA-ANF receptor), which generates cGMP, the major second messenger of ANF actions. A second class of receptors, named by us clearance receptors (C-ANF receptors), is involved in the removal of ANF from plasma by a process of receptor-mediated endocytosis. In vivo blockade of C-ANF receptors by small ligands increases plasma levels of ANF, a finding that is of potential therapeutic importance in the treatment of cardiovascular and renal diseases. After having elucidated the overall systemic role and cellular mechanisms of the clearance function of C-ANF receptors, we are presently investiÐgating the molecular mechanisms of this function by using recombinant DNA and mutagenesis techniques. We are also actively investigating the dynamics of ANF interaction with recombinant wild type and mutated GCA-ANF receptor to determine the molecular mechanisms by which ANF exerts its biological actions. In addition, studies of other members of the family of natriuretic peptides (BNP, CNP), and of angiotensin receptors are subjects of interest to the laboratory.