title: Initiation of remote microvascular preconditioning requires K(ATP) channel activity.
abstract: The purpose of this study was to investigate vascular preconditioning of individual microvascular networks. Prior work shows that exposure of downstream arterioles to specific agonists preconditions upstream arterioles so that they exhibit an altered local vasoactive response [remote microvascular preconditioning (RMP)]. We hypothesized that mitochondrial ATP-sensitive K+ (K(ATP)) channels were involved in stimulation of RMP. Arteriolar diameter (approximately 15 microm) was observed approximately 1,000 microm upstream of the remote exposure site in the cheek pouch of pentobarbital sodium-anesthetized (70 mg/kg) male hamsters (n = 104); all agonists were applied via micropipette. RMP was initiated by application of pinacidil (Pin), diazoxide (DZ), sodium nitroprusside (SNP), or bradykinin (BK) to the downstream vessel. After 15 min, RMP was apparent at the upstream observation site from testing of local vasoactive responses to L-arginine. Pin, DZ, SNP, and BK each stimulated RMP. To evaluate a specific role for mitochondrial K(ATP) channels in this response, 5-hydroxydecanoate was applied (via a 2nd pipette) during downstream stimulation with agonist. 5-Hydroxydecanoate blocked RMP initiated by Pin, DZ, or SNP, suggesting that mitochondrial K(ATP) channels are involved before SNP signal transduction. To verify this, we applied N(omega)-nitro-L-arginine during DZ or SNP stimulation. RMP was blocked during SNP, but not during DZ, stimulation. Thus stimulation of the RMP response requires mitochondrial K(ATP) channel activity after stimulation by nitric oxide donors.
authors.affiliation: Dept. of Biomedical Engineering, SUNY Stony Brook, Stony Brook, New York 11794, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Mabanta
authors.forename: Patrick
authors.initials: P
authors.lastname: Valane
authors.forename: Jonathan
authors.initials: J
authors.lastname: Borne
authors.forename: Mary D
authors.initials: MD
authors.lastname: Frame
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001120:Arginine; D001160:Arterioles / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D006224:Cricetinae; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D019194:Ischemic Preconditioning / Q000379:methods*; D054086:KATP Channels; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D020110:Pinacidil / Q000037:antagonists & inhibitors / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D018528:ATP-Binding Cassette Transporters; D003652:Decanoic Acids; D006880:Hydroxy Acids; D054086:KATP Channels; D020030:Nitric Oxide Donors; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D009599:Nitroprusside; C016276:8-bromocyclic GMP; C052853:5-hydroxydecanoic acid; D020110:Pinacidil; D001120:Arginine; D006152:Cyclic GMP; D000241:Adenosine; D003981:Diazoxide; D001920:Bradykinin