TY - JOUR
T1 - Mechanism of coronary microvascular responses to metabolic stimulation
AU - Embrey, Richard P.
AU - Brooks, Leonard A.
AU - Dellsperger, Kevin C.
N1 - Funding Information:
This work was supported by RO1 HL51308, American Heart Association Grant-in-Aid 91-15050). Dr. Dellsperger is an Established Investigator of the American Heart Association. We acknowledge the secretarial assistance of Ms. Cindy Evans in the preparation of this manuscript.
PY - 1997/7
Y1 - 1997/7
N2 - 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.
AB - 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.
KW - ATP-sensitive
KW - Arginine analogs
KW - Coronary microcirculation
KW - Dobutamine
KW - EDRF
KW - Endothelium
KW - Glibenclamide
KW - Intravital microscopy
KW - Nitric oxide
KW - Potassium channel
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U2 - 10.1016/S0008-6363(97)00096-5
DO - 10.1016/S0008-6363(97)00096-5
M3 - Article
C2 - 9302359
AN - SCOPUS:0030772551
SN - 0008-6363
VL - 35
SP - 148
EP - 157
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 1
ER -