REGULATION OF ATRIAL-NATRIURETIC-PEPTIDE RECEPTORS IN VASCULAR SMOOTH-MUSCLE CELLS - ROLE OF CGMP

We tested the hypothesis that intracellular guanosine 3',5'-cyclic mon ophosphate (cGMP) regulates atrial natriuretic peptide (ANP) receptors . The effect of chronic exposure to ANP, sodium nitroprusside (SNP), a nd 8-bromo-cGMP (8-BrcGMP) on ANP receptors and cGMP formation was det ermined 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 t he ANP C-receptor. In TASM, 24-h treatment with 1 muM atriopeptin (AP) III [rat ANP-(103-126)] caused a sixfold increase in basal cGMP level s, which were unaltered in CASM. In AP III-treated TASM, maximal bindi ng of I-125-labeled AP III (B(max)) was reduced 40% while affinity [di ssociation constant (K(D))] was unaltered. In CASM, B(max) and K(D) we re not affected. In treated TASM, washed free of AP III, acute dose-re sponse curves of cGMP to AP III were not different from that in untrea ted cells. In both TASM and CASM, basal cGMP levels were elevated and B(max) 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 B(max). These findings support the conclusion tha t elevated cGMP was necessary for ANP-induced downregulation of recept ors. The unaltered responsiveness of cGMP to AP III suggests the B-rec eptor was not altered and the reduced B(max) was due to decreased C-re ceptor.