URODILATIN - USE OF A NEW PEPTIDE IN INTE NSIVE-CARE

On the subject of natriuretic peptides there is a great deal of contro versy, and intensive research efforts have been made studying their ef fects on electrolyte homeostasis. In the early 1980s, a peptide that c aused diuresis, natriuresis, and had a relaxant effect on vascular smo oth muscle was discovered independently by several groups. This was th e breakthrough for the identification of natriuretic peptides, followe d by the characterisation of the aminoacid sequences of several specie s. Synthesis of the peptide, cloning of the encoding gene, identificat ion and characterisation of specific receptors, as well as the develop ment of antibodies and radioimmunoassays were rapidly accomplished. Re search on the immunohistochemistry of cardiodilatin/atrial natriuretic peptide (CDD/ANP) and the regulation of CDD/ANP gene expression led t o detection of the peptide in extra-atrial tissues. Later on, two new peptides were discovered brain natriuretic peptide (BNP) and C-type na triuretic peptide (CNP). These peptides share structural features with CDD/ANP with regard to their 17-amino-acid-exhibiting loop bridged by a disulfide bond. Another recently discovered peptide is urodilatin ( URO), a renal-borne new member of A-type natriuretic peptide. URO was isolated from human urine and consists of the same sequence as CDD/ANP , containing the 17-amino-acid residue loop of the circulating hormone with 4 additional amino acids located at the NH2-terminus of the pept ide. Regarding physiological actions, data strongly support a close as sociation between URO and urinary sodium excretion. The application of URO in animals revealed a stronger diuresis and natriuresis with a lo wer influence on arterial blood pressure compared to CDD/ANP-99-126. T hese results were encouraging for the use of URO in clinical trials as a tool to prevent acute renal failure (ARF) in patients following hea rt transplantation and for treatment of incipient ARF in patients foll owing liver transplantation. Summarising the results of these two stud ies, URO represents a new approach for not only prevention, but also f or treatment of ARF following organ transplantation. This opens up new possibilities for the treatment of ARF of other origins in intensive care medicine.