title: Intracellular acidification alters myogenic responsiveness and vasomotion of mouse middle cerebral arteries.
abstract: Intracellular pH (pHi) in the vascular wall modulates agonist-induced vasocontractile and vasorelaxant responses in mesenteric arteries, whereas effects on myogenic tone have been unsettled. We studied the role of Na(+),HCO3(-) cotransporter NBCn1 in mouse isolated middle cerebral arteries and the influence of pHi disturbances on myogenic tone. Na(+),HCO3(-) cotransport was abolished in arteries from NBCn1 knockout mice and steady-state pHi ∼0.3 units reduced compared with wild-type mice. Myogenic tone development was low under control conditions but increased on treatment with the NO-synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME). This effect of L-NAME was smaller in arteries from NBCn1 knockout than wild-type mice. Myogenic tone with L-NAME present was significantly lower in arteries from NBCn1 knockout than wild-type mice and was abolished by rho-kinase inhibitor Y-27632. The arteries displayed vasomotion, and this rhythmic contractile pattern was also attenuated in arteries from NBCn1 knockout mice. No differences in membrane potential or intracellular [Ca(2+)] were seen between arteries from NBCn1 knockout and wild-type mice. We propose that NO production and rho-kinase-dependent Ca(2+) sensitivity are reduced at low pHi in pressurized mouse middle cerebral arteries. This likely impedes the ability to adjust to changes in perfusion pressure and regulate cerebral blood flow.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Axel B K
authors.initials: AB
authors.lastname: Thomsen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Sukhan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Filip
authors.initials: F
authors.lastname: Aalbaek
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Aalkjaer
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Ebbe
authors.initials: E
authors.lastname: Boedtkjer
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D020768:Middle Cerebral Artery / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: C498904:Slc4a7 protein, mouse; D027982:Sodium-Bicarbonate Symporters; D002118:Calcium