title: A key role for Na+/K+-ATPase in the endothelium-dependent oscillatory activity of mouse small mesenteric arteries.
abstract: Oscillatory contractile activity is an inherent property of blood vessels. Various cellular mechanisms have been proposed to contribute to oscillatory activity. Mouse small mesenteric arteries display a unique low frequency contractile oscillatory activity (1 cycle every 10-12 min) upon phenylephrine stimulation. Our objective was to identify mechanisms involved in this peculiar oscillatory activity. First-order mesenteric arteries were mounted in tissue baths for isometric force measurement. The oscillatory activity was observed only in vessels with endothelium, but it was not blocked by L-NAME (100 microM) or indomethacin (10 microM), ruling out the participation of nitric oxide and prostacyclin, respectively, in this phenomenon. Oscillatory activity was not observed in vessels contracted with K+ (90 mM) or after stimulation with phenylephrine plus 10 mM K+. Ouabain (1 to 10 microM, an Na+/K+-ATPase inhibitor), but not K+ channel antagonists [tetraethylammonium (100 microM, a nonselective K+ channel blocker), Tram-34 (10 microM, blocker of intermediate conductance K+ channels) or UCL-1684 (0.1 microM, a small conductance K+ channel blocker)], inhibited the oscillatory activity. The contractile activity was also abolished when experiments were performed at 20 degrees C or in K+-free medium. Taken together, these results demonstrate that Na+/K+-ATPase is a potential source of these oscillations. The presence of alpha-1 and alpha-2 Na+/K+-ATPase isoforms was confirmed in murine mesenteric arteries by Western blot. Chronic infusion of mice with ouabain did not abolish oscillatory contraction, but up-regulated vascular Na+/K+-ATPase expression and increased blood pressure. Together, these observations suggest that the Na+/K+ pump plays a major role in the oscillatory activity of murine small mesenteric arteries.
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
authors.forename: F R C
authors.initials: FR
authors.lastname: Giachini
authors.forename: F S
authors.initials: FS
authors.lastname: Carneiro
authors.forename: V V
authors.initials: VV
authors.lastname: Lima
authors.forename: Z N
authors.initials: ZN
authors.lastname: Carneiro
authors.forename: M W
authors.initials: MW
authors.lastname: Brands
authors.forename: R C
authors.initials: RC
authors.lastname: Webb
authors.forename: R C
authors.initials: RC
authors.lastname: Tostes
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000201:enzymology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010042:Ouabain / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase