title: Decreased activity of the smooth muscle Na+/Ca2+ exchanger impairs arteriolar myogenic reactivity.
abstract: Arteriolar myogenic vasoconstriction occurs when stretch or increased membrane tension leads to smooth muscle cell (SMC) depolarization and opening of voltage-gated Ca(2+) channels. While the mechanism underlying the depolarization is uncertain a role for non-selective cation channels has been demonstrated. As such channels may be expected to pass Na(+), we hypothesized that reverse mode Na(+)/Ca(2+) exchange (NCX) may act to remove Na(+) and in addition play a role in myogenic signalling through coupled Ca(2+) entry. Further, reverse (Ca(2+) entry) mode function of the NCX is favoured by the membrane potential found in myogenically active arterioles. All experiments were performed on isolated rat cremaster muscle first order arterioles (passive diameter approximately 150 mum) which were pressurized in the absence of intraluminal flow. Reduction of extracellular Na(+) to promote reverse-mode NCX activity caused significant, concentration-dependent vasoconstriction and increased intracellular Ca(2+). This vasoconstriction was attenuated by the NCX inhibitors KB-R7943 and SEA 04000. Western blotting confirmed the existence of NCX protein while real-time PCR studies demonstrated that the major isoform expressed in the arteriolar wall was NCX1. Oligonucleotide knockdown (24 and 36 h) of NCX inhibited the vasoconstrictor response to reduced extracellular Na(+) while also impairing both steady-state myogenic responses (as shown by pressure-diameter relationships) and acute reactivity to a 50 to 120 mmHg pressure step. The data are consistent with reverse mode activity of the NCX in arterioles and a contribution of this exchanger to myogenic vasoconstriction.
authors.affiliation: School of Medical Sciences, RMIT University, Bundoora, Victoria 3083, Australia.
authors.forename: Hema
authors.initials: H
authors.lastname: Raina
authors.forename: Srikanth R
authors.initials: SR
authors.lastname: Ella
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hill
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology*; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000098:blood supply* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D019831:Sodium-Calcium Exchanger