F. Perez-vizcaino et al., Modulation of arterial Na+-K+-ATPase-induced [Ca2+](i) reduction and relaxation by norepinephrine, ET-1, and PMA, AM J P-HEAR, 45(2), 1999, pp. H651-H657
Citations number
29
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Na+-K+-ATPase plays a major role in regulating membrane potential and vascu
lar tone. We analyzed the modulation by norepinephrine (NE), endothelin-1 (
ET-1), and phorbol 12-myristate 13-acetate (PMA) of Na+-K+-ATPase-induced c
ytoplasmic free Ca2+ concentration ([Ca2+](i)) reduction and relaxation in
isolated endothelium-denuded piglet mesenteric arteries. KCl (0.2-8.8 mM)-i
nduced [Ca2+](i) reduction and relaxation in arteries incubated in K+-free
solution were used as functional indicators of Na+-K+-ATPase activity. KCl-
induced relaxations after exposure to K+-free solution were associated with
a reduction in [Ca2+](i), as measured by fura 2 fluorescence. However, KCl
reduced [Ca2+](i) below resting values, whereas force was reduced to near
resting values. NE, ET-1, and PMA inhibited the relaxant effects of KCl, an
d this effect was attenuated by the protein kinase C inhibitor staurosporin
e but not by the phospholipase A(2) inhibitor quinacrine. However, ET-1 and
PMA potentiated the [Ca2+](i)-reducing effect of KCl. In conclusion, ET-1,
PMA, and NE are functional inhibitors of Na+-K+-ATPase activity in endothe
lium-denuded piglet mesenteric arteries, even when the direct effect on the
enzyme activity may be stimulatory rather than inhibitory. This can be exp
lained because ET-1, PMA, and NE induce Ca2+ sensitization for smooth muscl
e contraction, and therefore relaxations do not parallel the reductions in
[Ca2+](i) after the activation of Na+-K+-ATPase.