Aging decreases vasoconstrictor responses of coronary resistance arterioles through endothelium-dependent mechanisms

Shipley, Robert D.; Muller‐Delp, Judy M.

doi:10.1016/j.cardiores.2004.11.005

Cited by 75 publications

(73 citation statements)

References 43 publications

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“…-dependent potassium channels [34] (Georgeon-Chartier, Morel, personal preliminary data), and basal NO level in endothelial cells [51]. Our results could help understand the effects of aging on cardiovascular pathological risks.…”

Section: +mentioning

confidence: 63%

Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries

Georgeon-Chartier

Menguy

Prévot

et al. 2012

Pflugers Arch - Eur J Physiol

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In cerebral arteries, alterations of vascular reactivity have been observed but not well molecularly characterized. Therefore, we have hypothesized that cerebrovascular reactivity could be modified by aging via a modification of Ca These results show that aging induces a decrease of contractility correlated with modifications of the expression of genes encoding Ca 2+ signaling toolkit. Globally, the amplitude of Ca 2+ signals was decreased, whereas their duration was increased by a defection of Ca 2+ store refilling.

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Section: +mentioning

confidence: 63%

Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries

Georgeon-Chartier

Menguy

Prévot

et al. 2012

Pflugers Arch - Eur J Physiol

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“…This is in agreement with results from a study showing that ET B receptor blockade had no effect on ET-1-induced constriction of coronary arterioles from young rats. 41 Taken together, these diverse findings may suggest heterogeneity among microvascular beds in whether ET-1 stimulation elicits endothelial ET Bmediated dilation, or that there may be activation of other signaling pathways for NO release secondary to ET-1 stimulation.…”

Section: Discussionmentioning

confidence: 97%

Role of Endothelium in Vasomotor Responses to Endothelin System and Protein Kinase C Activation in Porcine Retinal Arterioles

Potts

Bradley

et al. 2013

Investigative Ophthalmology & Visual Science

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PURPOSE. Endothelial cells synthesize vasodilator nitric oxide (NO) and vasoconstrictor endothelin-1 (ET-1) from NO synthase (eNOS) and endothelin-converting enzyme-1 (ECE-1), respectively. Protein kinase C (PKC) and Rho kinase (ROCK) are major signaling molecules mediating vasoconstriction. Although endothelial cells express eNOS, ECE-1, endothelin B (ET B ) receptors, PKC, and ROCK, their influences on ET-1-induced vasoconstriction remain elusive. We studied whether these endothelial signaling molecules modulate retinal arteriolar constriction to ET-1. METHODS.Porcine retinal arterioles were isolated and pressurized for vasomotor study, under conditions with intact or denuded endothelium, using videomicroscopic techniques. RESULTS.Retinal arterioles developed similar resting tone (»45% of maximum diameter) with or without endothelium. Endothelial denudation attenuated vasoconstriction to ET-1 precursor, big ET-1, by almost equal to 50%, but did not affect vasoconstrictions to ET-1, ET B agonist sarafotoxin S6c, or PKC activator phorbol-12, 13-dibutyrate (PDBu). The ROCK inhibitor H-1152 caused vasodilation, and abolished vasoconstrictions to ET-1 and PDBu independent of endothelium. With L-type voltage-operated calcium channel (L-VOCC) blocker nifedipine, PDBu-induced vasoconstriction was abolished and converted to NO-mediated vasodilation in the presence of endothelium. The ET-1-induced vasoconstriction was unaffected by NO released from endothelium during flow elevation.CONCLUSIONS. Endothelial and smooth muscle ECE-1 contribute equally to synthesis of vasoactive ET-1 in retinal arterioles, with nominal role of endothelial ET B receptors in vasoconstriction to ET-1. The PKC activation leads to endothelium-dependent NO-mediated vasodilation when smooth muscle contraction is ablated by L-VOCC blockade. Endothelial cells and NO appear to have modest roles in modulating ROCK-dependent vasoconstriction, and are insufficient to counteract smooth muscle contractions to ET-1 and PKC activation.

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“…Rats were anesthetized (isoflurane 5%-O 2 balance) and euthanized by excision of the heart, which was immediately placed in cold, filtered physiological saline solution (PSS; pH 7.4) containing (in mM) 145 NaCl, 4.7 KCl, 2.0 CaCl 2, 1.17 MgSO4, 1.2 NaH 2PO4, 5.0 glucose, 2.0 pyruvate, 0.02 EDTA, 3.0 MOPS buffer, and 1% bovine serum albumin. Resistance arterioles (Ͻ150 m) were isolated from the left anterior descending coronary artery distribution as previously described (35). Arterioles were cannulated on pipettes matched for size and resistance in a Lucite chamber that contained PSS equilibrated with room air.…”

Section: Methodsmentioning

confidence: 99%

Aging impairs flow-induced dilation in coronary arterioles: role of NO and H₂O₂

Kang¹,

Reyes²,

Muller‐Delp³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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The beneficial effects of nitric oxide (NO)-mediated vasodilation are quickly abolished in the presence of ROS, and this effect may be augmented with aging. We previously demonstrated an age-induced impairment of flow-induced dilation in rat coronary arterioles. Therefore, the purpose of this study was to determine the effects of O 2 Ϫ scavenging, as well as removal of H2O2, the byproduct of O 2 Ϫ scavenging, on flow-mediated dilation in coronary resistance arterioles of young (4 mo) and old (24 mo) male Fischer 344 rats. Flow increased NO and H 2O2 production as evidenced by enhanced diaminofluorescein and dichlorodihydrofluorescein fluorescence, respectively, whereas aging reduced flow-induced NO and H 2O2 production. Endothelium-dependent vasodilation was evaluated by increasing intraluminal flow (5-60 nl/s) before and after treatment with the superoxide dismutase mimetic Tempol (100 M), the H 2O2 scavenger catalase (100 U/ml), or Tempol plus catalase. Catalase reduced flowinduced dilation in both groups, whereas Tempol and Tempol plus catalase diminished vasodilation in young but not old rats. Tempol plus deferoxamine (100 M), an inhibitor of hydroxyl radical formation, reversed Tempol-mediated impairment of flow-induced vasodilation in young rats and improved flow-induced vasodilation in old rats compared with control. Immunoblot analysis revealed increases in endogenous superoxide dismutase, catalase, and nitrotyrosine protein levels with aging. Collectively, these data indicate that NO-and H 2O2-mediated flow-induced signaling decline with age in coronary arterioles and that elevated hydroxyl radical formation contributes to the age-related impairment of flow-induced vasodilation.reactive oxygen species; superoxide dismutase; hydroxyl radical; deferoxamine; nitric oxide; hydrogen peroxide INCREASING EVIDENCE INDICATES that aging contributes significantly to the development of ischemic heart disease. Vascular resistance increases, leading to impairments in coronary blood flow and flow reserve (15). Endothelial dysfunction similarly progresses with aging (4) and may be mediated by impaired nitric oxide (NO) activity (7, 21) or elevated oxidant stress (6, 10). Previous studies have demonstrated age-associated declines in flow-mediated dilation in coronary arterioles due to impaired phosphatidylinositol 3-kinase signaling (21) or elevated superoxide (O 2 Ϫ ) production (7). Because flow-induced vasodilation is inextricably linked to NO-mediated signaling, it is possible that other factors directly involved in the NO pathway may be altered with advancing age.In (6,7,12). Thus ROS production and scavenging are likely carefully modulated to produce appropriate flow-induced dilation. Therefore, the purpose of our study was 1) to investigate age-related changes in NO and H 2 O 2 signaling during flow-induced vasodilation and 2) to examine the effects of ROS scavenging on flow-mediated dilation in coronary arterioles. METHODSAnimals. All procedures in this study were approved by the Institutional Animal Care and U...

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Aging decreases vasoconstrictor responses of coronary resistance arterioles through endothelium-dependent mechanisms

Cited by 75 publications

References 43 publications

Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries

Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries

Role of Endothelium in Vasomotor Responses to Endothelin System and Protein Kinase C Activation in Porcine Retinal Arterioles

Aging impairs flow-induced dilation in coronary arterioles: role of NO and H₂O₂

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Aging decreases vasoconstrictor responses of coronary resistance arterioles through endothelium-dependent mechanisms

Cited by 75 publications

References 43 publications

Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries

Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries

Role of Endothelium in Vasomotor Responses to Endothelin System and Protein Kinase C Activation in Porcine Retinal Arterioles

Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2

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Aging impairs flow-induced dilation in coronary arterioles: role of NO and H₂O₂