Effects of atherosclerosis on the coronary microcirculation

Chilian, William M.; Dellsperger, Kevin C.; Layne, Susan M.; Eastham, Charles L.; Armstrong, M.A.; Marcus, Melvin L.; Heistad, D D

doi:10.1152/ajpheart.1990.258.2.h529

Cited by 68 publications

(35 citation statements)

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“…4,5,10,25 In the present study, we demonstrated for the first time the presence of endothelial dysfunction in isolated human coronary resistance vessels from patients with severe atherosclerosis. So far, the underlying reasons and the pathophysiological significance of endothelial dysfunction remain unclear.…”

Section: Physiological and Pathophysiological Implicationssupporting

confidence: 55%

Endothelial Dysfunction of Coronary Resistance Arteries Is Improved by Tetrahydrobiopterin in Atherosclerosis

et al. 2000

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Background-Tetrahydrobiopterin (BH4), an essential cofactor for the synthesis of NO, improves endothelial dysfunction after ischemia/reperfusion. Therefore, we hypothesized that reduction of BH4 is involved in the attenuation of endothelium-dependent vasodilation in atherosclerosis, and we investigated the effect of alterations of the BH4 level on the vasodilatory potential of coronary resistance vessels from humans and pigs with atherosclerosis. Methods and Results-Coronary arterioles were obtained from patients undergoing CABG (atherosclerosis group) or valve replacement (control group) and from pigs fed either a standard diet (control group) or atherogenic diet (atherosclerosis group). After isolation, vessels were cannulated, pressurized, and placed on the stage of an inverted microscope. Dose-response curves were investigated in response to the endothelium-dependent agonists histamine, serotonin, and acetylcholine (for pigs, substance P) and to the endothelium-independent agonist sodium nitroprusside (SNP) under control conditions and before and after incubation of the vessels with sepiapterin (substrate for BH4 synthesis). In vessels from patients and from animals with atherosclerosis, compared with vessels from the control groups, there was a significant (PϽ0.05) reduction of vasodilation to all tested endothelium-dependent agonists but not to SNP. After application of sepiapterin, the responses to the endothelium-dependent agonists but not to SNP were significantly improved in vessels from the atherosclerosis groups. Sepiapterin did not influence vascular reactivity in the control groups. Conclusions-Atherosclerosis severely compromises endothelial function of coronary resistance arteries. Administration of sepiapterin leads to a significant improvement of endothelium-dependent vasodilatation to different agonists in vessels from humans and pigs with atherosclerosis. Therefore, we conclude that a reduced availability of BH4 is involved in the development of endothelial dysfunction in atherosclerosis.

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Section: Physiological and Pathophysiological Implicationssupporting

confidence: 55%

Endothelial Dysfunction of Coronary Resistance Arteries Is Improved by Tetrahydrobiopterin in Atherosclerosis

et al. 2000

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“…The mechanisms underlying abnormal endothelium-dependent vascular relaxation in atherosclerosis may include decreased or abnormal production and/or release of endothelium-derived relaxing factor, destruction of endothelium-derived relaxing factor, and the concomitant release of constricting factors. 39,41 A recent clinical study suggests that in patients with atherosclerosis, production of endothelium-derived cyclooxygenase-dependent constricting factors contributes to the abnormal acetylcholine-mediated dilation of the peripheral artery, which has no atherosclerotic lesions. 45 In addition to renal artery stenosis induced by atherosclerosis, endothelial dysfunction may also contribute to renovascular hypertension in Apoe -/-animals.…”

Section: Apoementioning

confidence: 99%

Hypertension and Endothelial Dysfunction in Apolipoprotein E Knockout Mice

Yang¹,

Powell-Braxton²,

Ogaoawara³

et al. 1999

ATVB

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Abstract-Mice lacking ApoE (Apoe -/-) develop initially hypercholesterolemia and latterly atherosclerosis. This study examined hemodynamics and endothelial function in 6-week-old Apoe -/-mice with hypercholesterolemia only, 7.5-months-old Apoe -/-mice with both hypercholesterolemia and atherosclerosis, and age matched controls. One day after implantation of catheters into the carotid artery, arterial pressure was measured in conscious, unrestrained mice. Compared with the respective controls, there was a significant increase in arterial pressure and the ratio of left ventricular weight to body weight in 7.5-month-old Apoe

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“…This agrees with earlier studies of large coronary arteries of hypercholesterolemic rabbits 5 and the coronary circulation of atherosclerotic nonhuman primates. 15 The abnormal response to 5-HT of the PCs could be associated with endothelial dysfunction, in the form of either impaired release of EDRF or release of a constricting factor from the endothelium. In normal PC segments, we found that endothelial removal increased the maximum response to 5-HT, which is consistent with responses in porcine and canine PCs.…”

Section: Increased Vasoconstriction To Serotonin In Large Atheromatoumentioning

confidence: 99%

Effect of induced hypercholesterolemia in rabbits on functional responses of isolated large proximal and small distal coronary arteries.

Simonsen

Prieto

Mulvany

et al. 1992

Arterioscler Thromb

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We studied the effects of hypercholesterolemia on the vascular responses of proximal and distal parts of the rabbit coronary circulation in two consecutive studies. For 12 weeks, New Zealand White rabbits were fed a control diet or a diet with 1% cholesterol dissolved in either 3% coconut oil (study A) or ether (study B). Isolated proximal epicardial and distal intramyocardial coronary arteries from control and hypercholesterolemic rabbits were mounted for isometric tension recording in a double myograph. In study A for hypercholesterolemic rabbits (A=12), the maximal relaxation and sensitivity to acetylcholine (ACh) were significantly decreased in proximal coronary segments contracted with 30 mmol/1 potassium solution compared with segments from control rabbits (it=13). The only change observed in distal coronary segments was a slight decrease in relaxation in response to low ACh concentrations (10~* and 3 x 10~* mol/1). However, in study B for proximal coronary and distal coronary segments from hypercholesterolemic rabbits (n=13), the area under the ACh relaxation curve was increased compared with that of control r abbits (n = 12). Other parameters that were similarly affected in studies A and B include the following: 1) proximal coronary segments from hypercholesterolemic rabbits were more sensitive to sodium nitroprusside (SNP) than were those from control rabbits, but this was not true for distal coronary segments; 2) endothelial removal from arterial segments of control rabbits induced a significant increase in sensitivity and maximal relaxation to SNP of proximal coronary and distal coronary arteries; 3) in segments from hypercholesterolemic rabbits, the absence of endothelium did not alter the response of proximal coronary segments to SNP but did augment the relaxation of distal coronary segments to SNP; 4) the maximal response to 5-hydroxvtrvptamine in proximal coronary arteries from hypercholesterolemic rabbits was increased compared with those from control rabbits, whereas such changes were not observed in distal coronary arteries; and 5) histological examination showed the presence of atheromatous plaques in proximal coronary but not in distal coronary segments from treated animals. In conclusion, the present investigation demonstrates that induced hypercholesterolemia alters both the structure and function of proximal parts of the coronary circulation. In distal coronary arteries of hypercholesterolemic rabbits, the only change observed was an impaired endothelium-dependent cholinergie relaxation, but even this change appeared to be dependent on the manner in which cholesterol was added to the diet, although parallel studies are required to confirm this. (

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Effects of atherosclerosis on the coronary microcirculation

Cited by 68 publications

References 0 publications

Endothelial Dysfunction of Coronary Resistance Arteries Is Improved by Tetrahydrobiopterin in Atherosclerosis

Endothelial Dysfunction of Coronary Resistance Arteries Is Improved by Tetrahydrobiopterin in Atherosclerosis

Hypertension and Endothelial Dysfunction in Apolipoprotein E Knockout Mice

Effect of induced hypercholesterolemia in rabbits on functional responses of isolated large proximal and small distal coronary arteries.

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