Mechanism of coronary microvascular responses to metabolic stimulation

Richard P. Embrey, Leonard A. Brooks, Kevin C. Dellsperger

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Previous studies from our laboratory have shown that coronary microvascular dilation to increased myocardial oxygen consumption (MVO2) is greater in vessels < 100 μm. The mechanism responsible for this response is uncertain. Objectives: 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 increases in MVO2 will stimulate opening of the ATP-sensitive potassium channel. Methods: Changes in epicardial coronary microvascular diameters were measured in 9 dogs given N(G)-nitro-L-arginine (LNNA; 100 μM, topically), 7 dogs given glibenclamide (10 μM, topically) and 12 control (C) dogs during increases in metabolic demand using dobutamine (DOB, 10 μg/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 μm) 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 similar increases in MVO2. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)148-157
Number of pages10
JournalCardiovascular Research
Volume35
Issue number1
DOIs
StatePublished - Jul 1 1997
Externally publishedYes

Fingerprint

Glyburide
Dilatation
Nitric Oxide
KATP Channels
Dobutamine
Dogs
Arterioles
Lighting
Oxygen Consumption
Arginine
Hemodynamics
Hypertension
Control Groups

Keywords

  • Arginine analogs
  • ATP-sensitive
  • Coronary microcirculation
  • Dobutamine
  • EDRF
  • Endothelium
  • Glibenclamide
  • Intravital microscopy
  • Nitric oxide
  • Potassium channel

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Mechanism of coronary microvascular responses to metabolic stimulation. / Embrey, Richard P.; Brooks, Leonard A.; Dellsperger, Kevin C.

In: Cardiovascular Research, Vol. 35, No. 1, 01.07.1997, p. 148-157.

Research output: Contribution to journalArticle

Embrey, Richard P. ; Brooks, Leonard A. ; Dellsperger, Kevin C. / Mechanism of coronary microvascular responses to metabolic stimulation. In: Cardiovascular Research. 1997 ; Vol. 35, No. 1. pp. 148-157.
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abstract = "Previous studies from our laboratory have shown that coronary microvascular dilation to increased myocardial oxygen consumption (MVO2) is greater in vessels < 100 μm. The mechanism responsible for this response is uncertain. Objectives: 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 increases in MVO2 will stimulate opening of the ATP-sensitive potassium channel. Methods: Changes in epicardial coronary microvascular diameters were measured in 9 dogs given N(G)-nitro-L-arginine (LNNA; 100 μM, topically), 7 dogs given glibenclamide (10 μM, topically) and 12 control (C) dogs during increases in metabolic demand using dobutamine (DOB, 10 μg/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 μm) 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 similar increases in MVO2. Conclusion: 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.",
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