title: Regulation of Na+-K+-AtPase in rat aortas: pharmacological and functional evidence.
abstract: Electrogenic sodium pump (Na(+)-K(+)-ATPase) maintains intracellular ionic concentration and controls membrane potential, Therefore, we analyzed the modulation of Na(+)-K(+)-ATPase activity by the endothelium, cyclic AMP-protein kinase A (cAMP-PKA), protein kinase C (PKC) and nitric oxide-cyclic GMP-protein kinase G (NO-cGMP-PKG) in isolated rat thoracic aortas. The potassium-induced relaxation in arteries incubated in K(+)-free solution was used as a functional indicator of Na(+)-K(+)-ATPase activity for ounbain abolished the potassium-induced relaxation in rat aortas. Potasslium-induced relaxations after removal of the endothelium were moderately blunted in these preparations. In the presence of N(omega)-nitro-L-arginine methyl ester, but not indomethacin, the potassium-induced relaxation was also inhibited. Similar inhibitions of potassium-induced relaxations were observed in aortas treated with 8-bromo-cAMP and phorbol 12-myristate 13-acetate (PMA). Although inhibitors of PKA and PKC individually did not affect the potassium-induced relaxation, the combination of both inhibitors significantly potentiated that relaxation. In contrast to 8-bromo, cAMP and PMA, 8-bromo-cGMP enhanced the potassium-induced relaxation whereas 1H-[1,2,4}oxadiazolo[4,3-a]quinoxalin-1-one attenuated that relaxation. These results suggested that endothelium is a functional stimulator of the Na(+)-K(+)-ATPase activity. In addition, cAMP-PKA and PKC pathways inhibited the sodium pump while the NO-cGMP pathway stimulated this pump in the vascular bed.
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan, ROC.
authors.forename: Kao-Hsiang
authors.initials: KH
authors.lastname: Chen
authors.forename: Shiu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Wu
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011921:Rats, Inbred WKY; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009569:Nitric Oxide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester