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 systolic blood pressure, those with an uncontrolled systolic blood pressure (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.

Role of atrial natriuretic peptide in the dissociation between flow relations with ventricular mass and function in a community with volume-dependent hypertension

“…Participants gave informed, written consent. The present study design has previously been described ( 3 – 6 , 15 , 18 , 22 , 23 ). Briefly, in a cross-sectional community-based study, nuclear families of black African descent (Nguni and Sotho chiefdoms) with siblings older than 16 years of age were randomly recruited (population census figures of 2001) from the South West Township (SOWETO) of Johannesburg, South Africa.…”

“…Hypertension was defined as a mean office BP ≥ 140 mm Hg systolic or ≥90 mm Hg diastolic or the use of antihypertensive medication. Plasma concentrations of ANP were measured using an enzyme-linked immunosorbent assay (Elabscience Biotechnology Inc, Houston, Texas, USA) as previously described ( 6 ). Although, NTproANP is more stable and has a longer half-life than ANP, it has no known biological actions.…”

“…However, most studies conducted with models of volume overload have employed arteriovenous fistulae or aortic regurgitation ( 12 – 14 ) where the volume overload does not translate into a combined volume and pressure load. In contrast, in populations with sustained volume-dependent primary hypertension, a combined pressure and volume overload occurs ( 3 – 6 ). In this regard, in contrast to current notions of the determinants of left ventricular (LV) geometry, in populations with sustained volume-dependent primary hypertension, concentric LV geometry is determined as much by increased volume and pressure as is eccentric LV geometry ( 17 ).…”

“…Although the degree of the pressure load is strongly associated with LV dysfunction ( 18 ), whether the volume load produces similar effects on LV mass (LVM) and LV function in sustained volume-dependent hypertension, is unclear. In volume-dependent populations, circulating atrial natriuretic peptide (ANP) concentrations are enhanced ( 6 ), and preclinical ( 19 , 20 ) and clinical ( 21 ) studies indicate that ANP augments myocardial systolic and diastolic function, particularly in the presence of LV hypertrophy ( 19 ). Thus, it is possible that despite an adverse effect of volume load on pulse pressure (PP) and hence LVM, the increased release of ANP in volume overload states protects the LV from volume-induced effects on myocardial function.…”

“…To address this question in the present study conducted in a population with prevalent volume-dependent hypertension, we therefore evaluated whether volume-induced increases in PP produce differential effects on LVM and tissue Doppler indexes of myocardial function. We further assessed whether relationships between the enhanced ANP concentrations associated with the volume overload state ( 6 ) and myocardial function, in-part account for any dissociation between the impact of volume-dependent effects on LVM and function.…”