Contribution of Vasodilator Prostanoids and Nitric Oxide to Resting Flow, Metabolic Vasodilation, and Flow-Mediated Dilation in Human Coronary Circulation

Duffy, Stephen J.; Castle, Sally; Harper, Richard W.; Meredith, Ian T.

doi:10.1161/01.cir.100.19.1951

Cited by 174 publications

(127 citation statements)

References 50 publications

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“…Indeed, in general, endothelium-mediated (drug-and shear stress-stimulated) dilation of isolated coronary arteries is reduced in hypertensive humans 11,[53][54][55][56][57] and animals, 19,21,32,36,45,51,52,[58][59][60][61][62] while the endothelium-independent vasodilatory responses to sodium nitroprusside and adenosine are often unaltered. 21,32,45,55,63 There are exceptions to these general observations 18,33,50,[63][64][65][66] and the vessel type (conduit vs resistance artery), 45,57 the mode of precontraction, 33 and the vasodilator protocol 45,56,61,67 or eliminated 58,68,69 by inhibitors of eNOS in isolated coronary vessels from hypertensive animals, suggesting that NO remains an important component of vascular function even when its bioavailability is reduced in hypertension. In isolated pressurized coronary microvessels it was observed that removal of the endothelium increased the amount of myogenic constriction to a greater extent in SHR than in WKY over a wide pressure range.…”

Section: Nitric Oxide-mediated Vasomotor Function Of Isolated Coronarmentioning

confidence: 97%

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Levy

Chung²,

Kroetsch

et al. 2009

VHRM

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This review highlights a number of nitric oxide (NO)-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS) to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca 2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been studied extensively to establish mechanisms for sex differences in NO-dependent function. Genomic and nongenomic effects of estrogen on eNOS and direct and indirect antioxidant activities of estrogen are discussed as potential mechanisms of interest in coronary circulation that could have implications for sex-and estrogen status-dependent therapy for hypertension and coronary dysfunction. The current review identifies some important basic knowledge gaps and speculates on the potential clinical relevance of hypertension adaptations in factors regulating coronary NO function.

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Section: Nitric Oxide-mediated Vasomotor Function Of Isolated Coronarmentioning

confidence: 97%

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Levy

Chung²,

Kroetsch

et al. 2009

VHRM

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“…Ruocco et al (26) demonstrated COX inhibition with indomethacin did not alter coronary blood flow in response to an experimentally induced flow-limiting coronary artery stenosis in pigs. However, COX inhibition in patients with coronary artery disease causes coronary vasoconstriction (8,11), thus suggesting that vasodilator PGs may play a greater role in the regulation of coronary vasomotor control in chronic vs. acute ischemia and in blood vessels subjected to atherosclerotic disease processes. By contrast, we recently demonstrated that adenosine receptor inhibition with aminophylline blunts the compensatory vasodilator response in the contracting human forearm subjected to acute hypoperfusion and is independent of NO (3).…”

Section: H266 Cyclooxygenase Inhibition and Skeletal Muscle Hypoperfumentioning

confidence: 99%

Prostaglandins do not contribute to the nitric oxide-mediated compensatory vasodilation in hypoperfused exercising muscle

Casey

Joyner

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Casey DP, Joyner MJ. Prostaglandins do not contribute to the nitric oxide-mediated compensatory vasodilation in hypoperfused exercising muscle. Am J Physiol Heart Circ Physiol 301: H261-H268, 2011. First published May 2, 2011; doi:10.1152/ajpheart.00222.2011.-We tested the hypothesis that 1) prostaglandins (PGs) contribute to compensatory vasodilation in contracting human forearm subjected to acute hypoperfusion, and 2) the combined inhibition of PGs and nitric oxide would attenuate the compensatory vasodilation more than PG inhibition alone. In separate protocols, subjects performed forearm exercise (20% of maximum) during hypoperfusion evoked by intra-arterial balloon inflation. Each trial included baseline, exercise before inflation, exercise with inflation, and exercise after deflation. Forearm blood flow (FBF; ultrasound) and local (brachial artery) and systemic arterial pressure [mean arterial pressure (MAP); Finometer] were measured. In protocol 1 (n ϭ 8), exercise was repeated during cyclooxygenase (COX) inhibition (Ketorolac) alone and during Ke-In protocol 2 (n ϭ 8), exercise was repeated during L-NMMA alone and during L-NMMA-Ketorolac. Forearm vascular conductance (FVC; ml·min Ϫ1 · 100 mmHg Ϫ1 ) was calculated from FBF (ml/min) and local MAP (mmHg). The percent recovery in FVC during inflation was calculated as (steady-state inflation ϩ exercise value Ϫ nadir)/ [steady-state exercise (control) value Ϫ nadir] ϫ 100. In protocol 1, COX inhibition alone did not reduce the %FVC recovery compared with the control (no drug) trial (92 Ϯ 11 vs. 100 Ϯ 10%, P ϭ 0.83). However, combined COX-nitric oxide synthase (NOS) inhibition caused a substantial reduction in %FVC recovery (54 Ϯ 8%, P Ͻ 0.05 vs. Ketorolac alone). In protocol 2, the percent recovery in FVC was attenuated with NOS inhibition alone (69 Ϯ 9 vs. 107 Ϯ 10%, P Ͻ 0.01) but not attenuated further during combined NOS-COX inhibition (62 Ϯ 10%, P ϭ 0.74 vs. L-NMMA alone). Our data indicate that PGs are not obligatory to the compensatory dilation observed during forearm exercise with hypoperfusion.prostaglandins; blood flow; nitric oxide; vasodilation; exercise; hypoperfusion DURING ACUTE EXPERIMENTAL hypoperfusion, skeletal muscle blood flow is partially restored in the exercising forearm through local dilator mechanisms and/or a myogenic response (4, 5). Along these lines, nitric oxide synthase (NOS) inhibition blunts the magnitude of restoration of forearm blood flow (FBF) and vascular conductance (FVC) during exercise with acute hypoperfusion by 10 -20% (4). The fact that a substantial flow restoration still occurs despite NOS inhibition suggests that additional vasodilator signals are likely involved in this response.In general, prostaglandins (PGs) do not appear to contribute significantly to the exercise hyperemic response to dynamic contractions (9,16,20,29,31). These findings are based on little to no change in muscle blood flow following PG synthesis inhibition. However, PGs have been reported to be involved in the regulation of skeletal muscle ...

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“…Wilson & Kapoor (1993) and Duffy et al (1998) previously detected that inhibition of cyclooxygenase with aspirin or indomethacin decreased the resting FBF by 20-30%. Prostacyclin also contributes to metabolic vasodilation (Kilbom & Wennmalm, 1976;Duffy et al, 1999a) as well as to resting and metabolic vasodilation in coronary arteries (Duffy et al, 1999b).…”

Section: Effect Of Antagonists On Baseline Vascular Tonementioning

confidence: 99%

ATP‐induced vasodilation in human skeletal muscle

Ginneken

Meijer

Verkaik

et al. 2004

British J Pharmacology

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1 The purine nucleotide adenosine-5 0 -triphosphate (ATP) exerts pronounced effects on the cardiovascular system. The mechanism of action of the vasodilator response to ATP in humans has not been elucidated yet. The proposed endothelium-derived relaxing factors (EDRFs) were studied in a series of experiments, using the perfused forearm technique. 2 Adenosine 5 0 -triphosphate (0.2, 0.6, 6 and 20 nmol dl À1 forearm volume min À1 ) evoked a dosedependent forearm vasodilator response, which could not be inhibited by separate infusion of the nonselective COX inhibitor indomethacin (5 mg dl À1 min À1 , n ¼ 10), the blocker of Na þ /K þ -ATPase ouabain (0.2 mg dl À1 min À1 , n ¼ 8), the blocker of K Ca channels tetraethylammonium chloride (TEA, 0.1 mg dl À1 min À1 , n ¼ 10), nor by the K ATP -channel blocker glibenclamide (2 mg dl À1 min À1 , n ¼ 10). All blockers, except glibenclamide, caused a significant increase in baseline vascular tone. The obtained results might be due to compensatory actions of unblocked EDRFs. Combined infusion of TEA, indomethacin and L-NMMA (n ¼ 6) significantly increased the baseline forearm vascular resistance. The ATP-induced relative decreases in forearm vascular resistance were 4875, 6773, 8872, and 9272% in the absence and 2377, 6274, 8972, and 9371% in the presence of the combination of TEA, indomethacin and L-NMMA (Po0.05, repeated-measures ANOVA, n ¼ 6). A similar inhibition was obtained for sodium nitroprusside (SNP, Po0.05 repeated-measures ANOVA, n ¼ 6), indicating a nonspecific interaction due to the blocker-induced vasoconstriction. 3 ATP-induced vasodilation in the human forearm cannot be inhibited by separate infusion of indomethacin, ouabain, glibenclamide or TEA, or by a combined infusion of TEA, indomethacin, and L-NMMA. Endothelium-independent mechanisms and involvement of unblocked EDRFs, such as CO, might play a role, and call for further studies.

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Contribution of Vasodilator Prostanoids and Nitric Oxide to Resting Flow, Metabolic Vasodilation, and Flow-Mediated Dilation in Human Coronary Circulation

Cited by 174 publications

References 50 publications

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Prostaglandins do not contribute to the nitric oxide-mediated compensatory vasodilation in hypoperfused exercising muscle

ATP‐induced vasodilation in human skeletal muscle

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