Effect of the renal natriuretic peptide, ularitide, alone or combined with Vasopeptidase inhibitor, Omapatrilat, on experimental volume overload-induced congestive heart failure in rats (Ularitide/Omapatrilat in Congestive Heart Failure)

Abstract

Introduction: Ularitide is a synthetic form of renally derived natriuretic peptide (NP), urodilatin. Omapatrilat (OMA) is a Vasopeptidase inhibitor (VPI), acting by dual inhibition of both angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP), which degrades the NPs. Ularitide and OMA underwent evaluation for the management of hypertension and heart failure (HF). Aim: This study aimed to address the effect of ularitide and OMA in aortocaval fistula (ACF)induced congestive heart failure (CHF) in rats under various conditions of compensation (of clinical severity). Experimental protocol: Volume-overload CHF was induced in male albino rats by creating an infrarenal ACF. One week after fistula induction, ACF rats were randomized to compensated (Com) and decompensated (Decom) ACF groups and each further subdivided into ACF, ularitide and OMA/ularitide treated ACF groups. Sham was used as control. All treatment protocols were started one week after infrarenal ACF induction and continued for further two weeks. Three weeks after shunt induction, all animals were underwent assessment of cardiorenal and humoral functions. Renal outcome was measured by glomerular filtration rate (GFR), fractional excretion of sodium (F Na ), absolute urinary sodium excretion (U Na V), urine volume, plasma cystin C level and urinary cyclic 3 0 , 5 0 -guanosine monophosphate (cGMP). The humoral function was assessed by plasma renin activity (PRA), angiotensin II (Ang II), Aldosterone, and cGMP. Cardiac outcome was assessed by plasma atrial natriuretic peptide (ANP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) while total and relative heart, lung and liver weights were recorded.