Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

Duncker, Dirk J.; Beer, Vincent J. de; Merkus, Daphne

doi:10.1007/s11517-008-0315-1

Cited by 26 publications

(18 citation statements)

References 105 publications

(166 reference statements)

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“…Furthermore, PDE5 expression is attenuated compared with normal swine, which acts to maintain cGMP-mediated vasodilation in coronary resistance vessels. In combination with previous data from our laboratory, showing attenuation of endothelin type A-and angiotensin II type 1 receptor-mediated vasoconstriction in the remote myocardium after MI (12,40,42), the present study further supports the concept that attenuation of vasoconstrictor pathways serves to maintain coronary perfusion in the remodeled myocardium after MI.…”

Section: Discussionsupporting

confidence: 90%

Phosphodiesterase 5 inhibition-induced coronary vasodilation is reduced after myocardial infarction

Merkus

Visser

Houweling

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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DJ. Phosphodiesterase 5 inhibition-induced coronary vasodilation is reduced after myocardial infarction. Am J Physiol Heart Circ Physiol 304: H1370 -H1381, 2013. First published March 15, 2013 doi:10.1152/ajpheart.00410.2012The balance between the production and removal of cGMP in coronary vascular smooth muscle is of critical importance in determining coronary vasomotor tone and thus in the regulation of coronary blood flow. cGMP production by soluble guanylyl cyclase is activated by nitric oxide (NO), whereas cGMP breakdown occurs through phosphodiesterase 5 (PDE5). We hypothesized that myocardial infarction (MI) alters the balance between the production and removal of cGMP in the coronary vasculature and thereby alters the control of coronary vasomotor tone. Chronically instrumented swine with and without a 2-wk-old MI were exercised on a treadmill in the absence and presence of the PDE5 inhibitor EMD-360527 (300 g·kg Ϫ1 ·min Ϫ1 iv). Inhibition of PDE5 produced coronary resistance vessel dilation, which was more pronounced at rest than during exercise in normal swine. PDE5 gene expression was markedly reduced in coronary resistance vessels isolated from the remote myocardium of MI swine, which was accompanied by a similarly marked attenuation of coronary vasodilation by PDE5 inhibition in MI swine. The coronary vasoconstriction produced by inhibition of NO synthesis with N -nitro-L-arginine (20 mg/kg iv) was only slightly smaller in swine with MI. Interestingly, inhibition of NO synthesis reduced the vasodilator response to subsequent PDE5 inhibition in normal swine but not in MI swine. Conversely, PDE5 inhibition enhanced the coronary vasoconstriction produced by NO synthesis inhibition in normal swine but not in MI swine, suggesting that downregulation of PDE5 mitigated the loss of NO vasodilator influence. In conclusion, the expression and vasoconstrictor influence of PDE5 are markedly attenuated in coronary resistance vessels in the remote myocardium after MI, which appears to serve as a compensatory mechanism to mitigate the loss of NO vasodilator influence. coronary circulation; myocardial infarction; nitric oxide; phosphodiesterase 5; vasodilation LEFT VENTRICULAR (LV) function critically depends on an adequate oxygenation of the myocardium. Since myocardial O 2 extraction (ME O 2 ) is already high under resting conditions, any substantial increase in myocardial O 2 demand must be met by an increase in O 2 supply and hence an increase in coronary blood flow (CBF) (15,20). This tight matching of CBF to myocardial metabolism is the result of a delicate balance between a myriad of vasomotor signals stemming from cardiomyocytes, autonomic nerve terminals, and the endothelium (11,15,20,56).The endothelium-derived vasodilator nitric oxide (NO) produces coronary vasodilation through the activation of soluble guanylyl cyclase (sGC) and formation of cGMP in vascular smooth muscle (21). cGMP signaling is terminated through breakdown of cGMP by phosphodiesterase 5 (PDE5) and, to a lesser extent, by PDE1 (46). Th...

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Section: Discussionsupporting

confidence: 90%

Phosphodiesterase 5 inhibition-induced coronary vasodilation is reduced after myocardial infarction

Merkus

Visser

Houweling

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…Thus, MO 2 ex is maintained constant over a wide range of myocardial O 2 demands, indicating that changes in extravascular compression are compensated by changes in coronary vasomotor tone. In contrast, in MI swine, MO 2 ex increased with incremental levels of exercise, suggesting that the increased extravascular compressive forces (higher heart rate and LAP) were not fully compensated by a decrease in coronary vasomotor tone (15).…”

Section: Discussionmentioning

confidence: 79%

“…The increased extravascular compression combined with neurohumoral activation can impede myocardial perfusion. Indeed, the O 2 balance in the remodeled myocardium is perturbed after myocardial infarction (MI), particularly during exercise (15). Unexpectedly, however, coronary vasodilation in response to blockade of either ET A /ET B or AT 1 receptors was blunted in swine with MI compared with normal swine, suggesting that the vasoconstrictor influences of ET and ANG II were reduced (34,36).…”

mentioning

confidence: 99%

Integrative control of coronary resistance vessel tone by endothelin and angiotensin II is altered in swine with a recent myocardial infarction

Beer¹,

Sorop²,

Pijnappels³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Several studies have indicated an interaction between the renin-angiotensin (ANG II) system and endothelin (ET) in the regulation of vascular tone. Previously, we have shown that both ET and ANG II exert a vasoconstrictor influence on the coronary resistance vessels of awake normal swine. Here, we investigated whether the interaction between ANG II and ET exists in the control of coronary resistance vessel tone at rest and during exercise using single and combined blockade of angiotensin type 1 (AT(1)) and ET(A)/ET(B) receptors. Since both circulating ANG II and ET levels are increased after myocardial infarction (MI), we investigated if the interaction between these systems is altered after MI. In awake healthy swine, coronary vasodilation in response to ET(A)/ET(B) receptor blockade in the presence of AT(1) blockade was similar to vasodilation produced by ET(A)/ET(B) blockade under control conditions. In awake swine with a 2- to 3-wk-old MI, coronary vasodilator responses to individual AT(1) and ET(A)/ET(B) receptor blockade were virtually abolished, despite similar coronary arteriolar AT(1) and ET(A) receptor expression compared with normal swine. Unexpectedly, in the presence of AT(1) blockade (which had no effect on circulating ET levels), ET(A)/ET(B) receptor blockade elicited a coronary vasodilator response. These findings suggest that in normal healthy swine the two vasoconstrictor systems contribute to coronary resistance vessel control in a linear additive manner, i.e., with negligible cross-talk. In contrast, in the remodeled myocardium, cross-talk between ANG II and ET emerges, resulting in nonlinear redundant control of coronary resistance vessel tone.

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“…After MI, endothelial and neurohumoral control of coronary vasomotor tone is altered (12). To maintain perfusion of the hypertrophied remote myocardium after MI in the presence of endothelial dysfunction (reduced NO vasodilation), coronary flow reserve is recruited not only by increasing metabolic vasodilation via K ATP channel activation (35) but surprisingly also by suppression of endogenous vasoconstrictor influences of ET (7,34) and angiotensin II (7,32).…”

Section: Perspective and Conclusionmentioning

confidence: 99%

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

Beer

Taverne

Kuster

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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de Beer VJ, Taverne YJ, Kuster DW, Najafi A, Duncker DJ, Merkus D. Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction. Am J Physiol Heart Circ Physiol 301: H1080 -H1089, 2011. First published June 17, 2011 doi:10.1152/ajpheart.01307.2010 is associated with endothelial dysfunction resulting in an imbalance in endothelium-derived vasodilators and vasoconstrictors. We have previously shown that despite increased endothelin (ET) plasma levels, the coronary vasoconstrictor effect of endogenous ET is abolished after MI. In normal swine, nitric oxide (NO) and prostanoids modulate the vasoconstrictor effect of ET. In light of the interaction among NO, prostanoids, and ET combined with endothelial dysfunction present after MI, we investigated this interaction in control of coronary vasomotor tone in the remote noninfarcted myocardium after MI. Studies were performed in chronically instrumented swine (18 normal swine; 13 swine with MI) at rest and during treadmill exercise. Furthermore, endothelial nitric oxide synthase (eNOS) and cyclooxygenase protein levels were measured in the anterior (noninfarcted) wall of six normal and six swine with MI. eNOS inhibition with N -nitro-L-arginine (L-NNA) and cyclooxygenase inhibition with indomethacin each resulted in coronary vasoconstriction at rest and during exercise, as evidenced by a decrease in coronary venous oxygen levels. The effect of L-NNA was slightly decreased in swine with MI, although eNOS expression was not altered. Conversely, in accordance with the unaltered expression of cyclooxygenase-1 after MI, the effect of indomethacin was similar in normal and MI swine. L-NNA enhanced the vasodilator effect of the ETA/B receptor blocker tezosentan but exclusively during exercise in both normal and MI swine. Interestingly, this effect of L-NNA was blunted in MI compared with normal swine. In contrast, whereas indomethacin increased the vasodilator effect of tezosentan only during exercise in normal swine, indomethacin unmasked a coronary vasodilator effect of tezosentan in MI swine both at rest and during exercise. In conclusion, the present study shows that endothelial control of the coronary vasculature is altered in post-MI remodeled myocardium. Thus the overall vasodilator influences of NO as well as its inhibition of the vasoconstrictor influence of ET on the coronary resistance vessels were reduced after MI. In contrast, while the overall prostanoid vasodilator influence was maintained, its inhibition of ET vasoconstrictor influences was enhanced in post-MI remote myocardium. endothelin; nitric oxide; prostacyclin CONGESTIVE HEART FAILURE IS the only major cardiovascular disorder of which the incidence has increased over the past decade, which is principally due to a reduction in mortality associated with acute myocardial infarction (MI). Consequently, MI has become an increasingly important risk factor for the development of congestive heart failure (5). The loss of viable myocardial tissue and the consequent left ve...

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Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

Cited by 26 publications

References 105 publications

Phosphodiesterase 5 inhibition-induced coronary vasodilation is reduced after myocardial infarction

Phosphodiesterase 5 inhibition-induced coronary vasodilation is reduced after myocardial infarction

Integrative control of coronary resistance vessel tone by endothelin and angiotensin II is altered in swine with a recent myocardial infarction

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

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