Mechanisms of ATP-mediated vasodilation in humans: modest role for nitric oxide and vasodilating prostaglandins

Crecelius, Anne R.; Kirby, Brett S.; Richards, Jennifer C.; García, Lucy; Voyles, Wyatt F.; Larson, Dennis G.; Luckasen, Gary J.; Dinenno, Frank A.

doi:10.1152/ajpheart.00469.2011

Cited by 58 publications

(65 citation statements)

References 39 publications

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“…al. (8) found differences between methodologies when similar research questions were addressed. It is possible Doppler ultrasound measures a greater contribution of the cutaneous circulation compared with plethysmography.…”

Section: Discussionmentioning

confidence: 99%

β-Adrenergic-mediated vasodilation in young men and women: cyclooxygenase restrains nitric oxide synthase

Limberg

Johansson

Peltonen

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Limberg JK, Johansson RE, Peltonen GL, Harrell JW, Kellawan JM, Eldridge MW, Sebranek JJ, Schrage WG. ␤-Adrenergic-mediated vasodilation in young men and women: cyclooxygenase restrains nitric oxide synthase. Am J Physiol Heart Circ Physiol 310: H756 -H764, 2016. First published January 8, 2016 doi:10.1152/ajpheart.00886.2015.-We tested the hypothesis that women exhibit greater vasodilator responses to ␤-adrenoceptor stimulation compared with men. We further hypothesized women exhibit a greater contribution of nitric oxide synthase and cyclooxygenase to ␤-adrenergic-mediated vasodilation compared with men. Forearm blood flow (Doppler ultrasound) was measured in young men (n ϭ 29, 26 Ϯ 1 yr) and women (n ϭ 33, 25 Ϯ 1 yr) during intra-arterial infusion of isoproterenol (␤-adrenergic agonist). In subset of subjects, isoproterenol responses were examined before and after local inhibition of nitric oxide synthase [N Gmonomethyl-L-arginine (L-NMMA); 6 male/10 female] and/or cyclooxygenase (ketorolac; 5 male/5 female). Vascular conductance (blood flow Ϭ mean arterial pressure) was calculated to assess vasodilation. Vascular conductance increased with isoproterenol infusion (P Ͻ 0.01), and this effect was not different between men and women (P ϭ 0.41). L-NMMA infusion had no effect on isoproterenol-mediated dilation in men (P Ͼ 0.99) or women (P ϭ 0.21). In contrast, ketorolac infusion markedly increased isoproterenol-mediated responses in both men (P Ͻ 0.01) and women (P ϭ 0.04) and this rise was lost with subsequent L-NMMA infusion (men, P Ͻ 0.01; women, P Ͻ 0.05). ␤-Adrenergic vasodilation is not different between men and women and sex differences in the independent contribution of nitric oxide synthase and cyclooxygenase to ␤-mediated vasodilation are not present. However, these data are the first to demonstrate ␤-adrenoceptor activation of cyclooxygenase suppresses nitric oxide synthase signaling in human forearm microcirculation and may have important implications for neurovascular control in both health and disease.isoproterenol; blood flow; prostaglandin; sex differences; skeletal muscle NEW & NOTEWORTHYIn contrast to present thought, ␤-adrenergic-mediated vasodilation, and the independent contributions of nitric oxide synthase and cyclooxygenase, are remarkably similar in young men and women. These data are also the first to demonstrate ␤-adrenoceptor activation of the cyclooxygenase pathway actively suppresses nitric oxide synthase signaling in human forearm microcirculation.YOUNG WOMEN EXHIBIT LOWER cardiovascular disease risk compared with men (26). Part of this cardioprotection may be attributed to increased peripheral ␤-adrenergic-mediated vasodilation. For example, the relationship between sympathetic nervous system activity and total peripheral resistance observed in young men is present in women only during ␤-adrenoceptor blockade (16). Furthermore, when ␤-adrenoceptors are blocked, sympathetically-mediated vasoconstriction is increased in women but not in men (16). Consistent with this idea, young wom...

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Section: Discussionmentioning

confidence: 99%

β-Adrenergic-mediated vasodilation in young men and women: cyclooxygenase restrains nitric oxide synthase

Limberg

Johansson

Peltonen

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…To date, it is the only exogenously administered vasodilator with this property. However, the role of NO release as a contributor to ATP-mediated vasodilation is controversial with some studies reporting that NO release is not involved in ATP mediated vasodilation in human limbs and other studies showing a contribution (109,327,384,440). If NO is a major part of the ATP-mediated vasodilator response, then the question "why NOS inhibition does not cause a bigger decrement in exercise hyperemia?"…”

Section: Atpmentioning

confidence: 99%

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

Joyner

Casey

2015

Physiological Reviews

581

513

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LJoyner MJ, Casey DP. Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs. Physiol Rev 95: 549 -601, 2015; doi:10.1152/physrev.00035.2013.-This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans. The idea is that blood flow to the contracting muscles links oxygen in the atmosphere with the contracting muscles where it is consumed. In this context, we take a top down approach and review the basics of oxygen consumption at rest and during exercise in humans, how these values change with training, and the systemic hemodynamic adaptations that support them. We highlight the very high muscle blood flow responses to exercise discovered in the 1980s. We also discuss the vasodilating factors in the contracting muscles responsible for these very high flows. Finally, the competition between demand for blood flow by contracting muscles and maximum systemic cardiac output is discussed as a potential challenge to blood pressure regulation during heavy large muscle mass or whole body exercise in humans. At this time, no one dominant dilator mechanism accounts for exercise hyperemia. Additionally, complex interactions between the sympathetic nervous system and the microcirculation facilitate high levels of systemic oxygen extraction and permit just enough sympathetic control of blood flow to contracting muscles to regulate blood pressure during large muscle mass exercise in humans.

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“…For example, Maiorana et al (2001b) were unable to detect differences between a trained and an untrained group of middle-aged subjects. Metabolite build-up (including nitric oxide, ATP and prostaglandins) is known to influence the vascular responsiveness (Joannides et al 1995;Toth et al 2007;Kooijman et al 2008;Crecelius et al 2011), and it is possible that the 5 min occlusion duration may elicit a maximal dilatory response in all individuals. Therefore, a single long-duration occlusion period may not best reflect vascular differences between different subject populations.…”

Section: Introductionmentioning

confidence: 99%

Vascular responsiveness measured by tissue oxygen saturation reperfusion slope is sensitive to different occlusion durations and training status

McLay

Gilbertson

Pogliaghi

et al. 2016

Experimental Physiology

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Edited by: Philip J. Atherton New Findings r What is the central question of this study?Is the near-infrared spectroscopy-derived measure of tissue oxygen saturation (S tO 2 ) reperfusion slope sensitive to a range of ischaemic conditions, and do differences exist between trained and untrained individuals? r What is the main finding and its importance?The S tO 2 reperfusion rate is sensitive to different occlusion durations, and changes in the reperfusion slope in response to a variety of ischaemic challenges can be used to detect differences between two groups. These data indicate that near-infrared spectroscopy-derived measures of S tO 2 , specifically the reperfusion slope following a vascular occlusion, can be used as a sensitive measure of vascular responsiveness.The reperfusion rate of near-infrared spectroscopy-derived measures of tissue oxygen saturation (S tO 2 ) represents vascular responsiveness. This study examined whether the reperfusion slope of S tO 2 is sensitive to different ischaemic conditions (i.e. a dose-response relationship) and whether differences exist between two groups of different fitness levels. Nine healthy trained (T; age 25 ± 3 years; maximal oxygen uptake 63.4 ± 6.7 ml kg −1 min −1 ) and nine healthy untrained men (UT; age 21 ± 1 years; maximal oxygen uptake 46.6 ± 2.5 ml kg −1 min −1 ) performed a series of vascular occlusion tests of different durations (30 s, 1, 2, 3 and 5 min), each separated by 30 min. The S tO 2 was measured over the tibialis anterior using near-infrared spectroscopy, with the S tO 2 reperfusion slope calculated as the upslope during 10 s following cuff release. The reperfusion slope was steeper in T compared with UT at all occlusion durations (P < 0.05). For the T group, the reperfusion slopes for 30 s and 1 min occlusions were less than for all longer durations (P < 0.05). The reperfusion slope following 2 min occlusion was similar to that for 3 min (P > 0.05), but both were less steep than for 5 min of occlusion. In UT, the reperfusion slope at 30 s was smaller than for all longer occlusion durations (P < 0.05), and 1 min occlusion resulted in a reperfusion slope that was less steep than following 2 and 3 min (P < 0.05), albeit not different from 5 min (P > 0.05). The present study demonstrated that the reperfusion rate of S tO 2 is sensitive to different occlusion durations, and that changes in the reperfusion rate in response to a variety of ischaemic challenges can be used to detect differences in vascular responsiveness between trained and untrained groups.

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Mechanisms of ATP-mediated vasodilation in humans: modest role for nitric oxide and vasodilating prostaglandins

Cited by 58 publications

References 39 publications

β-Adrenergic-mediated vasodilation in young men and women: cyclooxygenase restrains nitric oxide synthase

β-Adrenergic-mediated vasodilation in young men and women: cyclooxygenase restrains nitric oxide synthase

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

Vascular responsiveness measured by tissue oxygen saturation reperfusion slope is sensitive to different occlusion durations and training status

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