Ischemic heart disease down-regulates angiotensin type 1 receptor mRNA in human coronary arteries

Wackenfors, Angelica; Emilson, Malin; Ingemansson, Richard; Edvinsson, Lars; Malmsjö, Malin

doi:10.1016/j.ejphar.2004.09.039

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…This paradoxical finding might be explained by a decrease in AT 1 and ET A receptor density in coronary arterioles. However, although one study (53) reported a decrease in AT 1 receptor mRNA, other studies have reported an increase in ET A receptor mRNA (54) in coronary arteries after MI as well as increased AT 1 (44) and ET A (27,57) receptor expression in whole myocardial samples from failing hearts. Importantly, however, these studies were either performed in large coronary arteries or in myocardial tissue comprised of both microvessels and myocardium, making data interpretation difficult.…”

Section: Discussionmentioning

confidence: 91%

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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Section: Discussionmentioning

confidence: 91%

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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“…This was largely expected, since it was unlikely for translation to have had enough time to produce suffi cient amounts of fi nished protein structure at this time. The of these receptors seen in heart failure and ischemic heart disease (14,15).…”

Section: Discussionmentioning

confidence: 99%

“…D16840) were designed as follows: it might contribute to pathological vasomotor function. The AT 1 -and AT 2 -receptors have been shown to be down-regulated in heart failure (14) and the AT 1 -receptor was also reduced in ischemic heart disease (15). The data regarding the regulation of ET-1 synthesis and release by shear stress forces on endothelial cells are controversial, since some reports have described a shear stress-dependent induction of ET-1 production, others have found no signifi cant changes in the ET-1 release, and still others have shown down-regulation.…”

Section: Real-time Reverse Transcription Polymerase Chain Reaction (Rmentioning

confidence: 99%

Increased perfusion pressure enhances the expression of endothelin (ET_B) and angiotensin II (AT₁, AT₂) receptors in rat mesenteric artery smooth muscle cells

Lindstedt

Zhang

et al. 2009

Blood Pressure

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In the present study, we hypothesized that changes in perfusion pressure result in altered expression of mRNA and protein encoding for the ETA-, ETB-, AT1- and AT2-receptors in rat mesenteric vessels. Segments of the rat mesenteric artery were cannulated with glass micropipettes, pressurized and luminally perfused in a perfusion chamber. After either exposure to no ("organ culture" (0 mmHg)), normal (85/75 mmHg) or high pressure (160/150 mmHg) at constant flow for 1-17 h, the vessel segments were snap frozen and real-time polymerase chain reaction was performed to quantify the ET- and AT-receptor mRNA content, or immersed in a fixative solution, dehydrated, frozen, cut in a cryostat and immunohistology stained for ET- and AT-receptor protein. The mRNA expressions of ETB and of AT2 were significantly enhanced in vessels exposed to high perfusion pressure, compared with normal and no perfusion pressure at 4 h. In concordance, AT1-, AT2- and ETB-receptor proteins were up-regulated at 17 h of high perfusion pressure. In conclusion, the results from our rat perfusion model suggest a more important role of shear stress than pure pressure alone and may serve as a surrogate model for studies designed to investigate hypertension mechanisms.

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“…It is also unlikely that a generalized loss of vasodilator capacity in the remote myocardium contributed to the blunted vasodilator response to irbesartan, because our laboratory (13) has previously shown that vasodilation produced by nitroprusside is unperturbed. Finally, although an increased AT 2 receptor expression could have acted to limit ANG II-induced vasoconstriction (29), this is unlikely because AT 2 mRNA was not altered in coronary arteries from patients with ischemic heart disease (38). Moreover, the dramatic increases in ANG II levels after irbesartan did not result in enhanced, but rather blunted, coronary vasodilation.…”

Section: Effect Of Angiotensin II On Coronary Vasomotor Tone After Mymentioning

confidence: 97%

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

Merkus¹,

Haitsma²,

Sorop³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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The renin-angiotensin system plays an important role in cardiovascular homeostasis by contributing to the regulation of blood volume, blood pressure, and vascular tone. Because AT(1) receptors have been described in the coronary microcirculation, we investigated whether ANG II contributes to the regulation of coronary vascular tone and whether its contribution is altered during exercise. Since the renin-angiotensin system is activated after myocardial infarction, resulting in an increase in circulating ANG II, we also investigated whether the contribution of ANG II to the regulation of vasomotor tone is altered after infarction. Twenty-six chronically instrumented swine were studied at rest and while running on a treadmill at 1-4 km/h. In 13 swine, myocardial infarction was induced by ligation of the left circumflex coronary artery. Blockade of AT(1) receptors (irbesartan, 1 mg/kg iv) had no effect on myocardial O(2) consumption but resulted in an increase in coronary venous O(2) tension and saturation both at rest and during exercise, reflecting coronary vasodilation. Despite increased plasma levels of ANG II after infarction and maintained coronary arteriolar AT(1) receptor levels, the vasodilation evoked by irbesartan was significantly reduced both at rest and during exercise. In conclusion, despite elevated plasma levels, the vasoconstrictor influence of ANG II on the coronary circulation in vivo is reduced after myocardial infarction. This reduction in ANG II-induced coronary vasoconstriction may serve to maintain perfusion of the remodeled myocardium.

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Ischemic heart disease down-regulates angiotensin type 1 receptor mRNA in human coronary arteries

Cited by 8 publications

References 34 publications

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

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

Increased perfusion pressure enhances the expression of endothelin (ET_B) and angiotensin II (AT₁, AT₂) receptors in rat mesenteric artery smooth muscle cells

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

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Ischemic heart disease down-regulates angiotensin type 1 receptor mRNA in human coronary arteries

Cited by 8 publications

References 34 publications

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

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

Increased perfusion pressure enhances the expression of endothelin (ETB) and angiotensin II (AT1, AT2) receptors in rat mesenteric artery smooth muscle cells

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

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Increased perfusion pressure enhances the expression of endothelin (ET_B) and angiotensin II (AT₁, AT₂) receptors in rat mesenteric artery smooth muscle cells