Biologically active atrial natriuretic peptides selectively activate Na/K/Cl cotransport in vascular smooth muscle cells.
Atrial natriuretic peptides (ANPs) cause vasorelaxation, natriuresis and diuresis. Although the precise mechanism of action for these biological activities is not known, it has been established that ANPs can bind to specific membrane receptors and can cause an increase in intracellular cyclic GMP (cGMP) levels. In previously published studies we have probed the mechanism of action of ANP and have shown that one consequence of ANP receptor-mediated increases in cGMP in vascular smooth muscle cells (VSMC) is stimulation of Na/K/Cl cotransport. Although others have suggested that ANPs may affect Na/H exchange and/or Na/K adenosine triphosphatase (ATPase) activity in various cells and tissues, the effect of ANPs on these other Na transport systems in VSMC is not known. Furthermore, the biological relevance of ANP-stimulation of Na/K/Cl cotransport in VSMC has not been established. The goal of the present study was to investigate whether ANPs selectively stimulate Na/K/Cl cotransport in VSMC and to determine whether effects on cotransport parallel biological activity. We tested the effect of six ANPs on Na/K/Cl cotransport, and of one ANP on Na/H exchange and on Na/K ATPase activity. It was found that ANPs stimulated Na/K/Cl cotransport but had no effect on Na/H exchange or on Na/K ATPase activity in VSMC. Biological activity of the ANPs was assayed by measuring the potencies for producing vasorelaxation of aortic rings and for stimulating an increase in intracellular cGMP in VSMC. The rank orders observed for the two biological activities agreed with the rank order for stimulation of Na/K/Cl cotransport.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Donnell
M E
ME
Department of Biological Chemistry and Structure, University of Health Sciences/Chicago Medical School, North Chicago, Illinois.
Bush
E N
EN
Holleman
W
W
Owen
N E
NE
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D014664:Vasodilation / Q000187:drug effects
D002712:Chlorides; D010446:Peptide Fragments; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D011188:Potassium