Attenuated Relationships Between Indexes of Volume Overload and Atrial Natriuretic Peptide in Uncontrolled, Sustained Volume-Dependent Primary Hypertension

Abstract

Background: Whether systolic blood pressure (SBP) control in sustained volume-dependent primary hypertension is associated with blunted ANP (atrial natriuretic peptide) relationships with indexes of volume load is unknown. Methods: Systemic hemodynamics (central pressure, echocardiographic aortic velocity and diameter measurements in the outflow tract), circulating ANP concentrations (ELISA assays) and glomerular and tubular function (24-hour urine collections [n=519]) were determined in a community of African ancestry (n=772). Results: As compared with those with a controlled SBP, those with an uncontrolled SBP (n=198) showed lower ANP concentrations ( P <0.005) despite higher stroke volume and cardiac output ( P <0.0001) and renal differences consistent with enhanced fluid retention. In those with a controlled SBP, fractional Na + excretion (FeNa + ; P <0.0005) and creatinine clearance (glomerular filtration rate; P <0.005) were inversely associated with ANP concentrations independent of confounders. Moreover, in those with a controlled SBP, stroke volume and cardiac output ( P <0.0001) were independently and positively associated with ANP concentrations. In addition, in those with a controlled SBP, ANP concentrations were independently and inversely associated with systemic vascular resistance (SVR; P <0.0001) and aortic characteristic impedance (Zc; P <0.005). By contrast, in those with uncontrolled SBP, no relationships between either stroke volume ( P >0.25), cardiac output ( P >0.29), FeNa + ( P >0.77), or glomerular filtration rate ( P >0.47) and ANP concentrations were noted. Furthermore, in those with an uncontrolled SBP, no relationships between ANP concentrations and SVR or Zc were observed ( P >0.34). Conclusions: In a population where primary hypertension is strongly volume-dependent, those with an uncontrolled SBP have an attenuated relationship between ANP and both renal and hemodynamic indexes of volume overload and the vascular effects of ANP.