Recently, substances with intrinsic natriuretic, diuretic and vasorelaxant activity have been isolated from the atrium of the heart. Studies of these substances, termed atrial natriuretic factors (ANF), have provided new information relevant to our understanding of the regulation of blood pressure and fluid volume. In addition, it is proposed that studies of these agents will lead to novel therapeutic approaches for treating hypertension and various edematous states. Although, biologically active ANF peptides of 21-28 amino acids have been isolated and sequenced, it is now apparent that these peptides reside in atrium predominately as a 126 amino acid precursor form (pro ANF). Due to the limited quantities available from natural sources, nothing is known about the physiological actions or metabolic fate, of pro ANF. Having isolated a cDNA clone encoding rate pre-pro ANF, we propose to express pro ANF in E. coli. Following purification, recombinant pro ANF will be tested for biological activity in model test systems. In addition, the circulatory fate of pro ANF will be examined. The proposed studies will provide relevant information about the general role and function of pro ANF and will test the concept that pro ANF has inherent therapeutic value for treating cardiovascular disease.
