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To elucidate the pathophysiological significance and the regulation of natriuretic peptide receptors (NP-R) in hypertension, we investigated the changes of NP-R in the lung, renal cortex and medulla using radioreceptor assay. We also examined the concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in the atria and ventricles and plasma ANP concentration by specific radioimmunoassays. Elevated plasma ANP level, decreased atrial ANP concentration and increased ventricular ANP and BNP contents were observed in the DOCA-salt group when compared with the control group (p &lt; 0.01). The ratio of BNP/ANP in the ventricle of the DOCA-salt rats was 50% of the control rats. The elevated plasma ANP secreted from the heart seems to reflect a defensive compensatory mechanism to counteract hypertension, and that ANP is the major natriuretic peptide secreted from the cardiac ventricle in DOCA-salt hypertensive rats. Scatchard plot analysis revealed that the maximal binding capacities (Bmax) of NP-R of the lung and renal cortex in DOCA-salt rats were significantly decreased from 71.0 +/- 10.4 to 38.4 +/- 5.9 (p &lt; 0.05) and from 32.7 +/- 1.8 to 21.7 +/- 0.4 (fmol/mg. protein) (p &lt; 0.01) compared with those in the control rats. The values of Bmax of the renal medulla between the two groups were not different. There was no significant change in the apparent dissociation constant (Kd) in the lung, renal cortex and medulla between the two groups. A competitive binding study using 125I- alpha-rANP1-28 and C-ANF4-23, a biologically silent clearance receptor (C-receptor) specific ligand, revealed that C-receptors are abundantly present in the renal cortex, while a relatively small quantity of C-receptor was detected in the renal medulla. In the lung, a substantial amount of C-receptor was detected. In the DOCA-salt treated rats, C-receptors were decreased in the lung and renal cortex compared with the control rats. These results indicate that the down-regulation of NP-R, especially C-receptor, was induced in the lung and renal cortex when plasma ANP levels were elevated in DOCA-salt hypertensive rats. In conclusion, our results suggest that down-regulation of C-receptor in the lung and kidney contributes to maintaining higher plasma ANP levels and maybe responsible for the counter-regulatory role of endogenous ANP in DOCA-salt rats. Our results show that the down-regulation of NP-R in the lung was larger than that in the kidney, suggesting that the lung may play a dominant role in the regulation of the clearance of ANP through C-receptors in vivo.

The Changes of Natriuretic Peptide Receptors (NP-R) for Lung and Kidney in DOCA-salt Hypertensive Rats