AJP - Heart and Circulatory Physiology, Vol 264, Issue 6 1753-H1759, Copyright © 1993 by American Physiological Society

ARTICLES

Regulation of atrial natriuretic peptide receptors in vascular smooth muscle cells: role of cGMP

L. M. Zhang, H. Tao and W. H. Newman
Medical Center of Central Georgia, Mercer University, Macon 31201.

We tested the hypothesis that intracellular guanosine 3',5'-cyclic monophosphate (cGMP) regulates atrial natriuretic peptide (ANP) receptors. The effect of chronic exposure to ANP, sodium nitroprusside (SNP), and 8-bromo-cGMP (8-BrcGMP) on ANP receptors and cGMP formation was determined in guinea pig thoracic aorta smooth muscle cells (TASM) and in coronary artery smooth muscle cells (CASM). TASM express both the ANP-activated guanylyl cyclase (B-receptor) and the clearance receptor (C-receptor) and respond to ANP with increased cGMP. CASM exhibit only the ANP C-receptor. In TASM, 24-h treatment with 1 microM atriopeptin (AP) III [rat ANP-(103-126)] caused a sixfold increase in basal cGMP levels, which were unaltered in CASM. In AP III-treated TASM, maximal binding of 125I-labeled AP III (Bmax) was reduced 40% while affinity [dissociation constant (KD)] was unaltered. In CASM, Bmax and KD were not affected. In treated TASM, washed free of AP III, acute dose-response curves of cGMP to AP III were not different from that in untreated cells. In both TASM and CASM, basal cGMP levels were elevated and Bmax was decreased by 6-h treatment with SNP. SNP did not alter the acute response of cGMP to AP III. In both cell types, 8-BrcGMP for 6 h caused reduction in Bmax. These findings support the conclusion that elevated cGMP was necessary for ANP-induced downregulation of receptors. The unaltered responsiveness of cGMP to AP III suggests the B-receptor was not altered and the reduced Bmax was due to decreased C-receptor.

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