Key result
Rats with myocardial infarction had elevated plasma ANP concentrations (462 vs 124 pg/ml, p<0.01) and reduced ANP binding densities in the inner renal medulla (2.93 vs 3.53 fmol/mg protein, p<0.01).
In a rat model of chronic heart failure, elevated plasma ANP levels correlate with decreased ANP receptor density in the renal medulla, suggesting receptor downregulation.
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Downregulated renal ANP receptors may blunt natriuresis in post-MI HF; leaves open therapeutic targeting in humans.
The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantitation of receptors was performed by computerized in vitro autoradiography with 125I-labeled alpha-rat ANP (1-28) as the radioligand. When compared with controls, rats with myocardial infarction had markedly elevated plasma immunoreactive ANP concentrations (462 +/- 82 versus 124 +/- pg/ml, p less than 0.01) and reduced densities of ANP binding in the inner renal medulla (2.93 +/- 0.19 versus 3.53 +/- 0.22 fmol/mg protein, p less than 0.01). Extensive myocardial infarction was associated with a significant decrease in receptor numbers in the inner medulla (33.6 +/- 5.7 versus 95.6 +/- 9.6 fmol/mg protein, p less than 0.01) without significantly altering the affinity constant (1.76 +/- 0.51 versus 1.03 +/- 0.15 x 10(9) M-1, p greater than 0.05). Right ventricular weight increased in proportion to infarct size (r = 0.71, p less than 0.01), and both were correlated with plasma immunoreactive ANP levels (r = 0.74, p less than 0.01 and r = 0.75, p less than 0.01, respectively). Binding densities in the inner medulla of rats with infarcts were negatively correlated with right ventricular weight, plasma immunoreactive ANP concentrations, and also with infarct size (r = -0.92, p less than 0.001; r = -0.78, p less than 0.001; r = -0.77, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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Tsunoda et al. (1988) studied Myocardial infarction / Chronic heart failure. Myocardial infarction vs. Controls was evaluated on Plasma immunoreactive ANP concentrations and ANP binding densities in the inner renal medulla (p=<0.01). Rats with myocardial infarction had elevated plasma ANP concentrations (462 vs 124 pg/ml, p<0.01) and reduced ANP binding densities in the inner renal medulla (2.93 vs 3.53 fmol/mg protein, p<0.01).
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