Regulation of Na-K-Cl cotransport in endothelial cells by atrial natriuretic factor

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49 Scopus citations


Many vasoactive agents have been shown to bind to specific receptors on endothelial cells. Among these is atrial natriuretic factor (ANF). Binding of ANF to endothelial cells has been demonstrated to induce elevation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). Other vasoactive agents have been shown to cause elevation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP), Ca, and diacylglycerol. However, the endothelial cell response that occurs subsequent to elevation of cGMP or other second messengers is not well understood. Recently, endothelial cells have been shown to possess a Na-K-Cl cotransport system that is stimulated by vasopressin and bradykinin and inhibited by isoproterenol. Thus it is possible that modulation of Na-K-Cl cotransport may play a role in the endothelial cell response to second messengers that are elevated by ANF and other vasoactive agents. This possibility was examined in the present study by evaluating the effects of a variety of vasoactive agents and their second messengers on endothelial cell Na-K-Cl cotransport. Cotransport was assessed as bumetanide-sensitive K influx in cultured bovine aortic endothelial cells. A number of agents were found to reduce Na-K-Cl cotransport, including ANF, acetylcholine, histamine, and norepinephrine. Cotransport was found to be stimulated by angiotensin II, as well as vasopressin and bradykinin. Na-K-Cl cotransport was also inhibited by elevation of intracellular cGMP or cAMP or by treatment of the cells with phorbol ester to activate protein kinase C. However, A23187-induced elevation of intracellular Ca caused stimulation of Na-K-Cl cotransport. Further investigation of the effect of ANF on cotransport revealed that inhibition of guanylate cyclase prevented the ANF-induced inhibition of cotransport but had no effect on 8-bromo-cGMP-induced inhibition, suggesting that elevation of intracellular cGMP mediates the effect of ANF on cotransport. This is the first demonstration of an endothelial cell response that occurs subsequent to ANF binding and elevation of intracellular cGMP. The results of the present study suggest that endothelial cell Na-K-Cl cotransport may play a role in mediating the effects of ANF and other vasoactive agents on the vasculature.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Issue number1
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology


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