Inhibitory action of norepinephrine on sodium transport in vascular smooth muscle cells in culture.
Cultured vascular smooth muscle cells from porcine aortas incubated in Na+ -free medium rapidly release their intracellular Na+ contents (Nai) (23 +/- 4% of baseline after 60 min incubation, mean +/- SEM of 18 experiments). Total Nai release was inhibited by 35-40% after addition of ouabain and by 60-70% after addition of ouabain + bumetanide. Norepinephrine inhibited ouabain and bumetanide-sensitives Na+ efflux with an IC50 of about 10(-9)-10(-8) M. Addition of the alpha-adrenergic agonist phenylephrine (10 microM) to the cells mimicked the inhibitory action of norepinephrine on Nai release. Conversely, the beta-adrenergic agonist isoproterenol was without effect on Nai release. Simultaneous addition of 10 microM norepinephrine and the alpha-adrenergic antagonist phentolamine prevented any effect of norepinephrine on the rate of Nai decline. In A-10 cultured vascular smooth muscle cells, the alpha-adrenergic agonist phenylephrine (10 microM) inhibited 40.0 +/- 8.1% of ouabain-sensitive Rb+ influx and 70.7 +/- 6.9% of bumetanide-sensitive Rb+ influx (mean +/- SEM of three experiments). 50% inhibition of bumetanide-sensitive Rb+ influx was obtained with about 5 x 10(-7) M of phenylephrine. Our results show that in vascular smooth muscle cells a [Na+, K+, Cl-]-cotransport system is able to catalyze outward Na+ movements (in Na+ -free media) of a similar order of magnitude to those of the Na+, K+ pump and that alpha-adrenergic stimulation markedly inhibits Na+ efflux (and Rb+ influx) through these two transport systems.
Tuck
M
M
INSERM U7, Hôpital Necker, Paris, France.
Hannaert
P
P
Jeanclos
E
E
Russo-Marie
F
F
Garay
R
R
D000818:Animals; D001011:Aorta / Q000166:cytology; D001693:Biological Transport, Active / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D002478:Cells, Cultured; D005665:Furosemide / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D013552:Swine
D002034:Bumetanide; D010656:Phenylephrine; D010042:Ouabain; D005665:Furosemide; D012964:Sodium; D007545:Isoproterenol; D012413:Rubidium; D009638:Norepinephrine