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Transmural difference in coronary arteriolar dilation to adenosine: effect of luminal pressure and K(ATP) channels
1Department of Medical Physiology, Cardiovascular Research Institute, The Texas A&M University System Health Science Center, College Station, Texas 77843-1114, USA.
Insights
Coronary arterioles dilate more to adenosine at lower pressures via ATP-sensitive K(+) channels. This pressure-dependent response may explain how blood flow is distributed in the heart during rest or stress.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Cardiac Metabolism
Background:
- Coronary blood flow is preferentially directed to the subendocardium by adenosine.
- During ischemia, coronary blood flow redistributes to the subepicardium, a mechanism not fully understood.
- Adenosine release during ischemia suggests a potential transmural difference in vasomotor response to adenosine.
Purpose of the Study:
- To investigate the transmural differences in coronary arteriolar vasomotor responsiveness to adenosine.
- To determine the role of ATP-sensitive K(+) (K(ATP)) channels in adenosine-mediated vasodilation across varying intraluminal pressures.
- To elucidate the mechanism behind adenosine-induced coronary blood flow redistribution.
Main Methods:
- Isolated pig subepicardial and subendocardial arterioles (60-120 µm) were pressurized in vitro (20-80 cmH2O).
- Vessel responses to adenosine and pinacidil (K(ATP) channel opener) were measured at different pressures.
- Effects of endothelium removal and glibenclamide (K(ATP) channel inhibitor) on vasodilation were assessed.
Main Results:
- Both subepicardial and subendocardial arterioles showed enhanced vasodilation to adenosine and pinacidil at lower intraluminal pressures (20 and 40 cmH2O).
- This enhanced vasodilation was endothelium-independent but abolished by glibenclamide, indicating smooth muscle K(ATP) channel activation.
- Adenosine-induced vasodilation was potentiated by pinacidil at lower pressures, mimicking the effect of pressure reduction.
Conclusions:
- Coronary microvascular dilation to adenosine is enhanced at lower intraluminal pressures through the activation of smooth muscle K(ATP) channels.
- The inherent pressure gradient across the ventricular wall may be a key factor in determining transmural coronary blood flow distribution.
- This mechanism likely plays a significant role in regulating coronary blood flow during both resting conditions and metabolic stress.
Abstract:
Coronary blood flow in the subendocardium is preferentially increased by adenosine but is redistributed to the subepicardium during ischemia in association with coronary pressure reduction. The mechanism for this flow redistribution remains unclear. Since adenosine is released during ischemia, it is possible that the coronary microcirculation exhibits a transmural difference in vasomotor responsiveness to adenosine at various intraluminal pressures. Although the ATP-sensitive K(+) (K(ATP)) channel has been shown to be involved in coronary arteriolar dilation to adenosine, its role in the transmural adenosine response remains elusive. To address these issues, pig subepicardial and subendocardial arterioles (60-120 micrometer) were isolated, cannulated, and pressurized to 20, 40, 60, or 80 cmH(2)O without flow for in vitro study. At each of these pressures, vessels developed basal tone and dilated concentration dependently to adenosine and the K(ATP) channel opener pinacidil. Subepicardial and subendocardial arterioles dilated equally to adenosine and pinacidil at 60 and 80 cmH(2)O luminal pressure. At lower luminal pressures (i.e., 20 and 40 cmH(2)O), vasodilation in both vessel types was enhanced. Enhanced vasodilatory responses were not affected by removal of endothelium but were abolished by the K(ATP) channel inhibitor glibenclamide. In a manner similar to reducing pressure, a subthreshold dose of pinacidil potentiated vasodilation to adenosine. In contrast to adenosine, dilation of coronary arterioles to sodium nitroprusside was independent of pressure changes. These results indicate that coronary microvascular dilation to adenosine is enhanced at lower intraluminal pressures by selective activation of smooth muscle K(ATP) channels. Since microvascular pressure has been shown to be consistently lower in the subendocardium than in the subepicardium, it is likely that the inherent pressure gradient in the coronary microcirculation across the ventricular wall may be an important determinant of transmural flow in vivo during resting conditions or under metabolic stress with adenosine release.