We previously demonstrated that vascular smooth muscle cells possess a prominent Na+-K+-Cl- cotransport system that can be markedly stimulated by elevations in levels of intracellular cyclic guanosine 3',5'-monophosphate (cGMP). Since others have shown that atrial natriuretic factor (ANF) can bind to specific membrane receptors and can enhance cGMP levels in vascular smooth muscle cells, we asked whether ANF could also stimulate Na+-K+-Cl- cotransport in vascular smooth muscle cells. It was discovered that rat atriopeptin III stimulated Na+-K+-Cl- cotransport of vascular smooth muscle cells in a concentration-dependent manner. In contrast, rat atriopeptin III had no effect on two other sodium transport systems known to be present in vascular smooth muscle cells (i.e., Na+-H+ exchange and Na+-K+-adenosine triphosphatase (ATPase)). These studies indicated that ANF selectively stimulates Na+-K+-Cl- cotransport of vascular smooth muscle cells. We then asked whether ANF-stimulated Na+-K+-Cl- cotransport was dependent upon the ability of ANF to enhance intracellular cGMP levels. When rat atriopeptin III-stimulated increases in cGMP were inhibited with the quinolinedione LY 83583, rat atriopeptin III could no longer stimulate Na+-K+-Cl- cotransport of vascular smooth muscle cells. Thus it appeared that the effects of ANF were dependent upon the ability of ANF to evaluate intracellular cGMP levels. Finally, we asked whether ANF effects on Na+-K+-Cl- cotransport were related to the biological activity of ANF. Using vasorelaxation of histamine-constricted aortic strips as an index of biological activity, we observed a tight correlation between the biological activity of six ANF analogues and their ability to stimulate Na+-K+-Cl- cotransport and to elevate intracellular cGMP levels of vascular smooth muscle cells. It appears that ANF interacts with a specific membrane receptor to elevate intracellular cGMP, which then leads to stimulation of Na+-K+-Cl- cotransport.
|Original language||English (US)|
|Issue number||5 II SUPPl.|
|State||Published - 1987|
ASJC Scopus subject areas
- Internal Medicine