Glomerular endothelial cells respond to calcium-mobilizing agonists with release of EDRF.
To determine whether glomerular endothelial cells (GEN) may play a role in the local control of glomerular function by releasing endothelium-derived relaxing factor (EDRF), the effect of several agonists on GEN cytosolic calcium concentration ([Ca2+]i) and GEN EDRF release was determined. Bradykinin, ATP, thrombin, and platelet-activating factor (PAF) all increased [Ca2+]i in GEN in a concentration-dependent manner, whereas serotonin, acetylcholine, phenylephrine, and endothelin-1 were without effect. Coincubation of glomerular mesangial cells (GMC) with GEN augmented mesangial cell guanosine 3',5'-cyclic monophosphate (cGMP) content five- to sixfold, Bradykinin elicited a further concentration-dependent increase in GMC cGMP content in the presence but not absence of GEN. The GEN-dependent bradykinin-stimulated GMC cGMP accumulation was abolished by hemoglobin and methylene blue, blunted by gossypol, and augmented by superoxide dismutase. Other agonists capable of augmenting GEN [Ca2+]i also stimulated GMC cGMP accumulation in the presence but not in the absence of GEN. Thus cultured GEN release a factor that stimulates cGMP accumulation in adjacent mesangial cells which has the pharmacological characteristics of EDRF.
Marsden
P A
PA
Harvard Center for the Study of Kidney Diseases, Boston, Massachusetts.
Brock
T A
TA
Ballermann
B J
BJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002196:Capillaries; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005470:Fluorometry / Q000379:methods; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism*; D009994:Osmolar Concentration
D009569:Nitric Oxide; D006152:Cyclic GMP; D002118:Calcium