Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor gamma ANP, that is gamma ANP-(1-25), and alpha ANP [gamma ANP-(99-126)], we studied the secretion of gamma ANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected gamma ANP-(1-25)-like immunoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 +/- 62 (+/- SE) pg/mL (174 +/- 21 pmol/L)]; the mean plasma alpha ANP-LI level at the same time in these subjects was 32.8 +/- 4.4 pg/mL (10.7 +/- 1.4 pmol/L). Gel permeation chromatographic analysis of plasma samples from normal subjects and patients with heart disease and chronic renal failure revealed two major components; one was alpha ANP, and the other was the 10K N-terminal gamma ANP fragment (N-peptide) resulting from the removal of alpha ANP (3K) from gamma ANP (13K). In addition, gamma ANP (13K), which possessed both gamma ANP-(1-25)-LI and alpha ANP-LI, and beta ANP, an antiparallel dimer of alpha ANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal gamma ANP fragment and alpha ANP (P less than 0.01) and almost equal step-ups in the coronary sinus plasma levels of the N-terminal gamma ANP fragment and alpha ANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI (17.4 +/- 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 +/- 7.1; P less than 0.01) suggest the slower clearance of the N-terminal gamma ANP fragment than alpha ANP and a role for the kidney in its degradation. Since the molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI in patients with cirrhosis (20.7 +/- 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal gamma ANP fragment is metabolized by the liver. In patients with heart disease, plasma gamma ANP-(1-25)-LI and alpha ANP-LI levels were higher in those with cardiac decompensation and were positively correlated with right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure, indicating cosecretion of the N-terminal gamma ANP fragment and alpha ANP in response to atrial stretch.(ABSTRACT TRUNCATED AT 400 WORDS)
The natriuretic peptide system comprises at least three ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) and three receptors, the ANP-A receptor, the ANP-B receptor, and the clearance (C) receptor. In the present study, the regulation of natriuretic peptide receptors by their ligands was investigated in cultured rat vascular smooth muscle cells (SMC). The treatment of vascular SMC with ANP, BNP, or CNP decreased the C-receptor density significantly, and the rank order of potency for this downregulation was CNP > ANP > BNP. This rank order was the same as that for guanosine 3',5'-cyclic monophosphate (cGMP) production by ANP, BNP, or CNP in vascular SMC and also the same as that for the ligand selectivity of the ANP-B receptor rather than the C-receptor. The incubation of vascular SMC with 8-bromoguanosine 3',5'-cyclic monophosphate significantly decreased the C-receptor density and its mRNA expression. These results suggest that the down-regulation of the C-receptor by natriuretic peptides is induced not by the binding of natriuretic peptides to the C-receptor but by the activation of the ANP-B receptor-cGMP pathway.
Although the water chemistry in saline lakes can differ drastically due to subtle differences in inflowing water conditions, the concentrations, distributions, and geochemical behaviors of trace elements in such environments are poorly understood. In this study, the influence of major‐ion chemistry on the trace element distribution in saline lakes is examined based on major and trace element concentrations and geochemical modeling in three carbonate‐rich saline lakes located in Mongolia and Turkey. The results are compared to data reported from other carbonate‐rich and carbonate‐depleted lakes. The concentrations of U and oxyanions (V, Mo, and W) in carbonate‐rich saline lakes are several orders of magnitude higher than their contributing rivers and seawater. By contrast, their concentrations in carbonate‐depleted saline lakes are lower than those in rivers and oceans. The high U concentrations in carbonate‐rich saline lakes are possibly attributed to the formation of (magnesium–)uranyl–carbonate complexes, and the high oxyanion concentrations are likely a result of the high pH of lake water preventing them from being adsorbed onto solid phases such as suspended particulate matter and sediment. Strontium and Ba concentrations are lower in carbonate‐rich saline lakes than in river water and seawater, but relatively higher in carbonate‐depleted lakes. Incorporation into aragonite and/or calcite, adsorption onto solid phases, and formation of carbonate minerals are possible mechanisms that may account for the lower concentrations of these elements in carbonate‐rich lakes. These results help elucidate the influence of water chemistry on trace element distribution in saline lakes.
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