Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction

Merkus, Daphne; Haitsma, David B.; Sorop, Oana; Boomsma, Frans; Beer, Vincent J. de; Lamers, Jos M. J.; Verdouw, Pieter D.; Duncker, Dirk J.

doi:10.1152/ajpheart.00861.2005

Cited by 25 publications

(34 citation statements)

References 39 publications

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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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“…To accommodate for the varying weights between animals and groups cardiac output, body O 2 consumption, PVC, PVR, SVC, and SVR were indexed to body weight. ET-1 plasma levels were determined as previously described (21,23).…”

Section: Discussionmentioning

confidence: 99%

“…Although ET secretion occurs predominantly on the abluminal side and plasma levels may therefore not adequately reflect interstitial ET concentrations, these findings point toward an interaction between ET and ANG II at the local vascular receptor level. For example, the approximately fivefold increase in ANG II plasma levels after irbesartan infusion (21) could have resulted in the activation of the AT 4 receptor, which has been shown to cause ET-dependent vasoconstriction in the basilar artery of rats (6). This is rather unlikely, however, as the activation of the AT 4 receptor on pulmonary endothelial cells has been shown to cause nitric oxide-dependent vasodilation (1).…”

Section: Integrated Regulation Of Resistance Vessel Tone By Et and Anmentioning

confidence: 99%

Integrated control of pulmonary vascular tone by endothelin and angiotensin II in exercising swine depends on gender

Beer

Graaff

Hoekstra

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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de Beer VJ, de Graaff HJ, Hoekstra M, Duncker DJ, Merkus D. Integrated control of pulmonary vascular tone by endothelin and angiotensin II in exercising swine depends on gender. Am J Physiol Heart Circ Physiol 298: H1976 -H1985, 2010. First published March 26, 2010 doi:10.1152/ajpheart.00459.2009The lungs are now recognized as an active metabolic organ that is a major determinant of the plasma concentrations of the vasoconstrictors endothelin (ET) and ANG II. Several studies have suggested a complex interaction between ET and ANG II in the systemic and coronary vascular beds that is different at rest and during exercise. To date, the interaction between these vasoconstrictor peptides has barely been investigated in relation to the pulmonary vascular bed. Consequently, we investigated the integrated control of pulmonary vasomotor tone by ET and ANG II in 24 chronically instrumented swine (15 female and 9 male) at rest and during graded treadmill exercise. In the systemic circulation, ANG II type 1 (AT1) receptor blockade with irbesartan and mixed ET A/ETB blockade with tezosentan each produced vasodilation. The systemic vasodilator effect of ETA/ETB blockade was enhanced after AT1 blockade in female swine, whereas a trend toward an increase was observed in male swine. In the pulmonary circulation, AT1 receptor blockade had no effect on pulmonary vascular tone in male swine, whereas it resulted in an unexpected increase in pulmonary vasomotor tone in female swine. ETA/ETB receptor blockade did not result in a decrease in pulmonary vasomotor tone at rest but produced a decrease in vasomotor tone during exercise in both genders. This pulmonary vasodilation by ETA/ETB receptor blockade was enhanced after prior AT1 blockade in female swine but not in male swine. In conclusion, in both the systemic and pulmonary circulation of female swine, ANG II inhibits the vasoconstrictor influence of ET. This interaction is gender specific. The observation that plasma ET levels were not altered by AT1 blockade in either gender suggests that the interaction between these vasoconstrictors occurs locally in the vasculature. microcirculation; exercise DURING EXERCISE, systemic vascular resistance (SVR) decreases by 70 -80% as a result of vasodilation of the exercising skeletal muscle. In contrast to the substantial decrease in SVR, pulmonary vascular resistance (PVR) decreases only modestly (20 -40%) during exercise (20). Consequently, the marked increase in cardiac output together with a small increase in left atrial pressure results in a significant increase in pulmonary arterial pressure, which serves to increase the homogeneity of pulmonary perfusion during exercise, thereby improving lung gas exchange (20,29). In addition to its obvious role in gas exchange, the lungs are increasingly recognized as an active metabolic organ contributing to the production and degradation of many vasoactive peptides. Two of such peptides that are produced and/or metabolized by the lungs are endothelin (ET) and ANG II. ET B receptors in the lungs m...

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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). The present study shows that the suppression of the vasoconstrictor influences of ET on the coronary resistance vessels in the remote remodeled myocardium is not due to NO, of which the overall vasodilator influence and the inhibition of ET influence were blunted.…”

Section: Perspective and Conclusionmentioning

confidence: 99%

“…12 for review). Furthermore, hemodynamic and neurohumoral abnormalities associated with LV dysfunction are exacerbated during exercise (24,32), which is accompanied by small perturbations in the myocardial O 2 balance as O 2 supply fails to match the increased O 2 demand (9,24).…”

mentioning

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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Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction

Cited by 25 publications

References 39 publications

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

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

Integrated control of pulmonary vascular tone by endothelin and angiotensin II in exercising swine depends on gender

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

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