The role of potassium in the metabolic control of coronary vascular resistance of the dog.

Murray, Paul A.; Belloni, Francis L.; Sparks, Harvey V.

doi:10.1161/01.res.44.6.767

Cited by 37 publications

(13 citation statements)

References 43 publications

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“…In this study, K ϩ -mediated vasodilation occurred through both inwardly rectifying K ϩ (K IR ) channels and Na ϩ -K ϩ -ATPase, similar to the mechanisms of K ϩ -mediated vasodilation in humans (17,21). Furthermore, these animal data substantiated early observations showing that changes in interstitial K ϩ concentration after brief muscle contraction have the appropriate magnitude and time course to have a significant involvement in the hyperemic response (26,35,39,50,53,54) and that smooth muscle vascular hyperpolarization may be essential to observe rapid vasodilation (33). Whether K ϩ -mediated vasodilation contributes to contraction-induced rapid vasodilation in humans is unknown.…”

supporting

confidence: 84%

“…Unfortunately, in our human forearm model, we were not able to inhibit K ϩ efflux from contracting muscle, and thus we are limited in the conclusions we are able to make regarding the source of K ϩ , as it could derive from skeletal muscle, as suggested by Armstrong and colleagues, or alternatively from small-and intermediate-conductance Ca 2ϩ -activated K ϩ channels on endothelial cells (28). K ϩ is an attractive candidate for the stimulus of rapid vasodilation as the time course is appropriate, it causes hyperpolarization via stimulation of both K IR and Na ϩ -K ϩ -ATPase, and, if originating from contracting skeletal muscle, would serve as a feedforward mechanism that couples rapid vasomotor responses with muscle activation (9,22,53). Additionally, an animal study (9) has reported that K ϩ -mediated vasodilation is most often transient in nature, and this may in part contribute to the distinct temporal pattern of the response.…”

Section: Potential Stimuli For Vasodilation After a Single Muscle Conmentioning

confidence: 99%

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Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle

Crecelius

Kirby

Luckasen

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Crecelius AR, Kirby BS, Luckasen GJ, Larson DG, Dinenno FA. Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle. Am J Physiol Heart Circ Physiol 305: H29-H40, 2013. First published May 3, 2013 doi:10.1152/ajpheart.00298.2013.-A monophasic increase in skeletal muscle blood flow is observed after a brief single forearm contraction in humans, yet the underlying vascular signaling pathways remain largely undetermined. Evidence from experimental animals indicates an obligatory role of vasodilation via K ϩ -mediated smooth muscle hyperpolarization, and human data suggest little to no independent role for nitric oxide (NO) or vasodilating prostaglandins (PGs). We tested the hypothesis that K ϩ -mediated vascular hyperpolarization underlies the rapid vasodilation in humans and that combined inhibition of NO and PGs would have a minimal effect on this response. We measured forearm blood flow (Doppler ultrasound) and calculated vascular conductance 10 s before and for 30 s after a single 1-s dynamic forearm contraction at 10%, 20%, and 40% maximum voluntary contraction in 16 young adults. To inhibit K ϩ -mediated vasodilation, BaCl2 and ouabain were infused intraarterially to inhibit inwardly rectifying K ϩ channels and Na ϩ -K ϩ -ATPase, respectively. Combined enzymatic inhibition of NO and PG synthesis occurred via N G -monomethyl-L-arginine (L-NMMA; NO synthase) and ketorolac (cyclooxygenase), respectively. In protocol 1 (n ϭ 8), BaCl 2 ϩ ouabain reduced peak vasodilation (range: 30 -45%, P Ͻ 0.05) and total postcontraction vasodilation (area under the curve, ϳ55-75% from control) at all intensities. Contrary to our hypothesis, L-NMMA ϩ ketorolac had a further impact (peak: ϳ60% and area under the curve: ϳ80% from control). In protocol 2 (n ϭ 8), the order of inhibitors was reversed, and the findings were remarkably similar. We conclude that K ϩ -mediated hyperpolarization and NO and PGs, in combination, significantly contribute to contraction-induced rapid vasodilation and that inhibition of these signaling pathways nearly abolishes this phenomenon in humans.hyperemia; exercise; potassium THE REGULATION of skeletal muscle hyperemia during muscle contractions is complex and involves a variety of signals that control both the arteriovenous perfusion pressure gradient and arteriolar caliber (10, 13). In an attempt to isolate the local mechanisms underlying exercise hyperemia, early experiments used a single brief muscle contraction to allow for contractioninduced hyperemia without the continuous interruption of the blood flow response or further stimulus for hyperemia, as occurs with repeated contractions (16). In this regard, the single contraction model can serve as a tool to examine feedforward mechanisms of hyperemia that are largely independent of changes in tissue oxidative metabolism (48). The typical response is characterized by an intensity-dependent, rapid, monophasic increase in blood flow that occurs immediately (within one cardiac cycle) after contraction, achieves full magni...

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confidence: 84%

Section: Potential Stimuli For Vasodilation After a Single Muscle Conmentioning

confidence: 99%

Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle

Crecelius

Kirby

Luckasen

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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show abstract

“…5 This is in agreement with our present finding in porcine coronary subepicardial arterioles that KCl-induced dilation is sensitive to Ba 2ϩ . Interestingly, the K ϩ -induced vasodilation has been suggested to be one of the mechanisms involved in the metabolic regulation of coronary blood flow because the increased K ϩ concentration during metabolic activation 10 or stress 11 is sufficient to evoke coronary vasodilation.…”

Section: Discussionmentioning

confidence: 99%

Activation of Barium-Sensitive Inward Rectifier Potassium Channels Mediates Remote Dilation of Coronary Arterioles

et al. 2001

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Background-Conducted vasodilation seems to be critical for the functional distribution of blood flow in the skeletal muscle microcirculation. However, this vasoregulatory phenomenon has not been documented in the coronary microcirculation, and its underlying mechanism remains elusive. Because potassium ions are potent metabolic vasodilators in the heart, by activating vascular inward rectifier K ϩ (K ir ) channels, we tested the hypothesis that coronary arterioles exhibit remote vasodilation through activation of this type of channel. Methods and Results-Porcine coronary arterioles were isolated, cannulated, and pressurized for in vitro study. Vessels dilated concentration-dependently to extraluminal KCl (5 to 20 mmol/L), bradykinin, adenosine, pinacidil, and sodium nitroprusside. A K ir channel blocker, BaCl 2 (30 mol/L), inhibited vasodilatory responses to KCl and bradykinin but not to adenosine, pinacidil, or nitroprusside. In a flow chamber, localized administration of bradykinin, adenosine, and KCl to the downstream end of the arterioles caused Ϸ80% dilation at the site of drug application (local site) and also produced 30% to 60% dilation at the upstream end of arterioles (remote site). Nitroprusside produced a similar dilation at the local site but failed to initiate remote vasodilation. In the presence of Ba 2ϩ , adenosine still dilated the local site, but the local dilations to bradykinin and KCl and the remote dilations to adenosine, bradykinin, and KCl were inhibited. Conclusions-We demonstrated that some modes of local vasodilation can be conducted to remote sites in coronary arterioles and that local and remote dilations can occur through different vasodilatory mechanisms. Activation of K ir channels seems critical for some agonist-induced local vasodilations and also for the initiation and/or transmission of signals causing remote vasodilation. Key Words: vasodilation Ⅲ physiology Ⅲ ion channels Ⅲ potassium Ⅲ microcirculation I n the skeletal muscle microcirculation, it has been shown that vasomotor responses elicited at one location (direct local response) can result in changes in vessel diameter at remote sites (conducted response). 1 Conducted vasomotor responses have been considered a result of changes in membrane potential through cell-cell electrical conduction along the vessel wall. 2 Although this conducted response has been described in a number of tissues and has been suggested to play an important role in the integrative coordination of blood flow distribution during increased metabolic demand, 3 it remains unclear whether this vasomotor response also exists in the heart. In addition, the underlying mechanisms involved in the propagation of vasodilation have not been elucidated.A possible mechanism for remote dilations in microvessels could involve K ϩ channels because they play a central role in the maintenance and regulation of the membrane potential in smooth muscle cells. 4 In excitable cells, the release of K ϩ during metabolic activation can contribute to flow recruitment through m...

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“…26 Interstitial volume variations are to be expected with changes in flow, both in control and with adenosine, by variation of capillary pressure 27 but also with saline infusion by decreasing plasma oncotic pressure. Also, the time course of DTF variation, being slower than intravascular volume variations, 28 is consistent with this hypothesis.…”

Section: Possible Mechanisms Of Increasing Dtfmentioning

confidence: 99%

Prolonged Diastolic Time Fraction Protects Myocardial Perfusion When Coronary Blood Flow Is Reduced

et al. 1999

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Background-Because coronary blood flow is impeded during systole, the duration of diastole is an important determinant of myocardial perfusion. The aim of this study was to show that coronary flow modulates the duration of diastole at constant heart rate. The increase in DTF at low pressure may be explained by a decrease in interstitial volume at low pressure, which either decreases the preload of the myocytes or reduces the buffer capacity for ions determining repolarization, thereby causing an earlier onset of relaxation. Conclusions-Because the largest increase in DTF occurs at pressures below the autoregulatory range when blood flow to the subendocardium is closely related to DTF, modulation of DTF by coronary blood flow can provide an important regulatory mechanism to match supply and demand of the myocardium when vasodilatory reserve is exhausted. (Circulation. 1999;100:75-81.) Methods and Results-In

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The role of potassium in the metabolic control of coronary vascular resistance of the dog.

Cited by 37 publications

References 43 publications

Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle

Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle

Activation of Barium-Sensitive Inward Rectifier Potassium Channels Mediates Remote Dilation of Coronary Arterioles

Prolonged Diastolic Time Fraction Protects Myocardial Perfusion When Coronary Blood Flow Is Reduced

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