Role of endothelium-derived nitric oxide in stimulation of Na(+)-K(+)-ATPase activity by endothelin in rabbit aorta

Abstract

An endothelium-derived factor with the properties of nitric oxide (NO) has recently been implicated in the regulation of basal Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in vascular smooth muscle. To determine whether this factor also plays a role in the stimulation of ouabain-sensitive (OS) 86Rb uptake by specific agonists, studies were carried out using rabbit aortic rings. In endothelium-intact rings incubated for 3 h with Krebs-Henseleit solution containing 5.5 mM glucose, endothelin (ET) caused a concentration-dependent increase in OS 86Rb uptake (maximal increase = 205%, with 100 nM ET). Incubation with phenylephrine (Phe; 0.1 and 1 microM) or phorbol 12,13-dibutyrate (PDBu; 0.1 microM), under the same conditions, increased OS 86Rb uptake by 128, 144, and 140%, respectively. Removal of endothelium before incubation decreased the ability of ET to stimulate OS 86Rb uptake by 38-45%, but it did not diminish the stimulation of OS 86Rb uptake by Phe or PDBu. An increase in the concentration of glucose from 5.5 to 44 mM diminished ET-stimulated OS 86Rb uptake by 50% in endothelium-intact rings but had no effect on Phe- or PDBu-induced increases in OS 86Rb uptake. Addition of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 0.3 mM) to the medium decreased ET-stimulated OS 86Rb uptake by 40%. Guanosine 3',5'-cyclic monophophate (cGMP) formation in endothelium-intact rings was also increased (65%) by ET but not by Phe or PDBu. The increase in cGMP by ET was totally inhibited by L-NMMA or endothelium denudation.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperglycemia increases endothelial superoxide that impairs smooth muscle cell Na+-K+-ATPase activity

“…This represents an attractive hypothesis, because previous data indicate that the endothelium exerts considerable influence over vascular Na ϩ -K ϩ -ATPase activity. In particular, we have previously demonstrated that endothelium-derived NO stimulates Na ϩ -K ϩ -ATPase activity in rabbit aorta (10,12). Because superoxide and NO combine readily in a diffusion-limited reaction (20) to form peroxynitrite, a compound with limited NO bioactivity, it is reasonable to speculate that hyperglycemia-induced superoxide limits the action of NO that is necessary for Na ϩ -K ϩ -ATPase activity.…”

“…The activity of Na ϩ -K ϩ -ATPase was determined by ouabain-sensitive 86 Rb ϩ uptake of aortic rings as described previously (10,12). Ouabain (0.1 mM) was added to the incubation medium 10 min before addition of 86 RbCl (2 Ci/ml).…”

“…In addition to the control of vascular tone, there is evidence that NO also plays a role in the regulation of basal Na ϩ -K ϩ -ATPase activity in arterial tissue (10,11). Hyperglycemia inhibits Na ϩ -K ϩ -ATPase activity in rabbit aorta, and this defect is related to diminished synthesis or bioactivity of NO (10,12).…”

“…Hyperglycemia inhibits Na ϩ -K ϩ -ATPase activity in rabbit aorta, and this defect is related to diminished synthesis or bioactivity of NO (10,12). Excess vascular superoxide is known to impair NO bioactivity in diabetes (13); however, the role of superoxide in modulating NO-mediated control of Na ϩ -K ϩ -ATPase activity in hyperglycemia is not known.…”

Contribution of Endogenous Endothelin-1 to the Maintenance of Vascular Tone: Role of Nitric Oxide

“…34], Also, abundant evidence indi cates that ETs and sarafotoxins activate for mation of NO and cyclic guanosine mono phosphate via the ETB receptor in a variety of tissues, including cultured bovine and rat en dothelial cells [35. 36], isolated rabbit aortic strips [37], and rat kidneys [35,36], Finally, hypoxia, NO inhibitors, and blockade of ETb receptors increase production and/or release of ET-I, in contrast to the decrease in ET-1 production reported with the increase in NO and oxygen [38][39][40][41][42][43]. These results indicate close interdependency between different ET receptors located on endothelium and vascu lar smooth muscle and the NO pathway.…”