Abstract
The mechanism of reactive hyperemia remains unknown. We hypothesized that reactive hyperemia was related to the opening of ATP-sensitive potassium channels during coronary occlusion. The resulting hyperpolarization of the smooth muscle cell plasma membrane might reduce calcium influx through voltage-dependent calcium channels and result in relaxation of smooth muscle tone and vasodilation. In eight open-chest, anesthetized dogs, 30-second coronary occlusions resulted in an average flow debt repayment of 200 ± 41%. After low-dose (0.8 μmol/min) and high-dose (3.7 μmol/min) infusion of intracoronary glibenclamide, flow debt repayment fell to 76 ± 14% and 50 ± 8%, respectively (p <0.05 compared with control for both). The decline in flow debt repayment was due to a signficant reduction both in maximum coronary conductance during reactive hyperemia and in its duration. In addition, there was a significant decline in the sensitivity of the coronary circulation to adenosine-induced vasodilation after glibenclamide. While more variable, there was no overall change in the sensitivity of the coronary vasculature to acetylcholine-induced vasodilation after glibenclamide. We conclude that reactive hyperemia is determined in a large part by the ATP-sensitive potassium channel, probably through its effect on membrane potential and voltage-sensitive calcium channels. Because reactive hyperemia was never fully abolished at the highest doses of glibenclamide tested, it is possible that additional mechanisms are involved in the genesis of this complex phenomenon.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 618-622 |
| Number of pages | 5 |
| Journal | Circulation Research |
| Volume | 69 |
| Issue number | 3 |
| State | Published - 1991 |
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Keywords
- ATP-sensitive potassium channels
- Coronary blood flow
- Reactive hyperemia
- Voltage-dependent calcium channels
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation. / Aversano, Thomas R; Ouyang, Pamela; Silverman, H.
In: Circulation Research, Vol. 69, No. 3, 1991, p. 618-622.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation
AU - Aversano, Thomas R
AU - Ouyang, Pamela
AU - Silverman, H.
PY - 1991
Y1 - 1991
N2 - The mechanism of reactive hyperemia remains unknown. We hypothesized that reactive hyperemia was related to the opening of ATP-sensitive potassium channels during coronary occlusion. The resulting hyperpolarization of the smooth muscle cell plasma membrane might reduce calcium influx through voltage-dependent calcium channels and result in relaxation of smooth muscle tone and vasodilation. In eight open-chest, anesthetized dogs, 30-second coronary occlusions resulted in an average flow debt repayment of 200 ± 41%. After low-dose (0.8 μmol/min) and high-dose (3.7 μmol/min) infusion of intracoronary glibenclamide, flow debt repayment fell to 76 ± 14% and 50 ± 8%, respectively (p <0.05 compared with control for both). The decline in flow debt repayment was due to a signficant reduction both in maximum coronary conductance during reactive hyperemia and in its duration. In addition, there was a significant decline in the sensitivity of the coronary circulation to adenosine-induced vasodilation after glibenclamide. While more variable, there was no overall change in the sensitivity of the coronary vasculature to acetylcholine-induced vasodilation after glibenclamide. We conclude that reactive hyperemia is determined in a large part by the ATP-sensitive potassium channel, probably through its effect on membrane potential and voltage-sensitive calcium channels. Because reactive hyperemia was never fully abolished at the highest doses of glibenclamide tested, it is possible that additional mechanisms are involved in the genesis of this complex phenomenon.
AB - The mechanism of reactive hyperemia remains unknown. We hypothesized that reactive hyperemia was related to the opening of ATP-sensitive potassium channels during coronary occlusion. The resulting hyperpolarization of the smooth muscle cell plasma membrane might reduce calcium influx through voltage-dependent calcium channels and result in relaxation of smooth muscle tone and vasodilation. In eight open-chest, anesthetized dogs, 30-second coronary occlusions resulted in an average flow debt repayment of 200 ± 41%. After low-dose (0.8 μmol/min) and high-dose (3.7 μmol/min) infusion of intracoronary glibenclamide, flow debt repayment fell to 76 ± 14% and 50 ± 8%, respectively (p <0.05 compared with control for both). The decline in flow debt repayment was due to a signficant reduction both in maximum coronary conductance during reactive hyperemia and in its duration. In addition, there was a significant decline in the sensitivity of the coronary circulation to adenosine-induced vasodilation after glibenclamide. While more variable, there was no overall change in the sensitivity of the coronary vasculature to acetylcholine-induced vasodilation after glibenclamide. We conclude that reactive hyperemia is determined in a large part by the ATP-sensitive potassium channel, probably through its effect on membrane potential and voltage-sensitive calcium channels. Because reactive hyperemia was never fully abolished at the highest doses of glibenclamide tested, it is possible that additional mechanisms are involved in the genesis of this complex phenomenon.
KW - ATP-sensitive potassium channels
KW - Coronary blood flow
KW - Reactive hyperemia
KW - Voltage-dependent calcium channels
UR - http://www.scopus.com/inward/record.url?scp=0026076853&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026076853&partnerID=8YFLogxK
M3 - Article
C2 - 1651815
AN - SCOPUS:0026076853
VL - 69
SP - 618
EP - 622
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 3
ER -