Hemodynamic effects of chronic urotensin II administration in animals with and without aorto-caval fistula

Urotensin II (UTII) is a potent vasoactive peptide. Recent studies have demonstrated increased expression of both UTII and its receptor (UTR) expression in end-stage congestive heart failure (CHF), but it is unclear whether UTII and UTR are late stage markers of decompensation, or earlier adaptive responses. The purpose of this study was to measure the effects of chronic UTII administration in normal and volume overloaded animals. Chronic 4 weeks administration of UTII produced decreases in hemodynamic function in animals not subjected to volume overload while returning function to control levels in animals with overload. Expression levels of calcium regulatory proteins phospholamban (PLN), sarcoplasmic reticulum Ca2+ ATPase (SERCA2), and Na+/Ca2+ exchanger (NCX) were measured to determine if administration of UTII resulted in aberrant Ca2+ handling. Changes in protein expression revealed that UTII influenced Ca2+ handling proteins in normal animals although these changes are not seen in the volume overload.