title: Mechanism of coronary microvascular responses to metabolic stimulation.
abstract: Previous studies from our laboratory have shown that coronary microvascular dilation to increased myocardial oxygen consumption (MVO2) is greater in vessels < 100 microns. The mechanism responsible for this response is uncertain.
  
  
  OBJECTIVE
  We tested the hypothesis that microvascular dilation to increased MVO2 is mediated by nitric oxide (NO). Since NO release may occur in response to increased shear, we also tested the hypothesis that metabolic byproducts released in response to increase in MVO2 will stimulate opening of the ATP-sensitive potassium channel.
  
  
  METHODS
  Changes in epicardial coronary microvascular diameters were measured in 9 dogs given NG-nitro-L-arginine (LNNA; 100 microM, topically), 7 dogs given glibenclamide (10 microM, topically) and 12 control (C) dogs during increases in metabolic demand using dobutamine (DOB, 10 micrograms/kg/min, i.v.) with rapid atrial pacing (PAC, 300 bpm). Diameters of arterioles were measured using intravital microscopy coupled to stroboscopic epi-illumination.
  
  
  RESULTS
  During the protocol, MVO2 increased to a similar degree in both experimental groups (LNNA and glibenclamide). Baseline hemodynamics and coronary microvascular diameters were similar between the two experimental groups and their respective control groups. In the presence of LNNA, coronary arteriolar (< 100 microns) dilation (% change from baseline) was impaired during the protocol (DOB: vehicle 18 +/- 5, LNNA 2 +/- 2 [P < 0.05]; DOB + RAP: vehicle 40 +/- 11, LNNA 6 +/- 2% [P < 0.05]). In contrast, glibenclamide did not impair coronary microvascular responses to increased MVO2 despite increases in MVO2.
  
  
  CONCLUSIONS
  This study indicates that coronary microvascular dilation in response to increased metabolic stimulation using dobutamine in conjunction with rapid pacing is mediated through a nitric-oxide-dependent mechanism and not ATP-sensitive potassium channels. These results may have important implications in pathological disease states where nitric oxide mechanisms are impaired, such as diabetes and hypertension.
authors.affiliation: Department of Surgery, University of Iowa, Iowa City 52242, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Embrey
authors.forename: L A
authors.initials: LA
authors.lastname: Brooks
authors.forename: K C
authors.initials: KC
authors.lastname: Dellsperger
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002304:Cardiac Pacing, Artificial; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D026902:Potassium Channel Blockers; D013268:Stimulation, Chemical; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D019335:Nitroarginine; D004280:Dobutamine; D019001:Nitric Oxide Synthase; D005905:Glyburide