Cyclooxygenase inhibition augments central blood pressure and aortic wave reflection in aging humans

Barnes, Jill N.; Casey, Darren P.; Hines, Casey N.; Nicholson, Wayne T.; Joyner, Michael J.

doi:10.1152/ajpheart.00032.2012

Cited by 13 publications

(17 citation statements)

References 48 publications

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“…Because we infused a nonselective inhibitor of cyclooxygenase, it is likely that vasodilating prostaglandins were also inhibited, and this may contribute to the rise in MAP observed at rest in healthy subjects (35). Ketorolac could also raise arterial stiffness and central BP, which has been shown in previous studies (4,5).…”

Section: Discussionmentioning

confidence: 64%

Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease

Müller

Drew

Ross

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Muller MD, Drew RC, Ross AJ, Blaha CA, Cauffman AE, Kaufman MP, Sinoway LI. Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease. Am J Physiol Heart Circ Physiol 309: H523-H528, 2015. First published June 8, 2015 doi:10.1152/ajpheart.00267.2015.-Prostanoids are produced during skeletal muscle contraction and subsequently stimulate muscle afferent nerves, thereby contributing to the exercise pressor reflex. Humans with peripheral arterial disease (PAD) have an augmented exercise pressor reflex, but the metabolite(s) responsible for this augmented response is not known. We tested the hypothesis that intravenous injection of ketorolac, which blocks the activity of cyclooxygenase, would attenuate the rise in mean arterial blood pressure (MAP) and heart rate (HR) evoked by plantar flexion exercise. Seven PAD patients underwent 4 min of single-leg dynamic plantar flexion (30 contractions/min) in the supine posture (workload: 0.5-2.0 kg). MAP and HR were measured on a beat-by-beat basis; changes from baseline in response to exercise were determined. Ketorolac did not affect MAP or HR at rest. During the first 20 s of exercise with the most symptomatic leg, ⌬MAP was significantly attenuated by ketorolac (2 Ϯ 2 mmHg) compared with control (8 Ϯ 2 mmHg, P ϭ 0.005), but ⌬HR was similar (6 Ϯ 2 vs. 5 Ϯ 1 beats/min). Importantly, patients rated the exercise bout as "very light" to "fairly light," and average pain ratings were 1 of 10. Ketorolac had no effect on perceived exertion or pain ratings. Ketorolac also had no effect on MAP or HR in seven age-and sex-matched healthy subjects who performed a similar but longer plantar flexion protocol (workload: 0.5-7.0 kg). These data suggest that prostanoids contribute to the augmented exercise pressor reflex in patients with PAD. PERIPHERAL ARTERIAL DISEASE (PAD) is a form of atherosclerosis that preferentially affects the lower extremity. Because leg blood flow is impaired in PAD, it is not surprising that dynamic exercise, such as walking, provokes pain in the calf, thigh, or buttocks, termed "intermittent claudication." Clinical exercise testing (e.g., the Bruce treadmill protocol) also causes a large increase in blood pressure (BP) in PAD patients, and studies (10, 11) have linked this augmented pressor response to cardiovascular morbidity and mortality. In recent years, our laboratory has focused on BP control in patients with PAD. Specifically, we found that 1) the BP response to single-leg dynamic plantar flexion exercise was augmented in PAD patients compared with healthy control subjects; 2) the pressor response occurred at very low workloads and before the onset of pain; 3) the pressor response correlated with the anklebrachial index (ABI), suggesting that disease severity plays a role; and 4) intravenous infusion of ascorbic acid lowered the pressor response to exercise in PAD (13,28). To date, the mechanisms for these findings are largely unknown. Understanding BP regulation during exercise in PAD ...

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Section: Discussionmentioning

confidence: 64%

Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease

Müller

Drew

Ross

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…In a previous study, we found that INDO augmented central blood pressure and aortic wave reflection in older individuals (Barnes et al . ). These changes in central haemodynamics, in conjunction with the slightly attenuated response to RH after INDO in older adults in the present study, reinforce the theory that older individuals have a limited ability to compensate for the acute haemodynamic shifts induced by INDO.…”

Section: Discussionmentioning

confidence: 97%

“…Taken together, it appears that COX inhibition has unfavourable effects on both central haemodynamics (Barnes et al . ) and peripheral vascular responses to RH in older adults. Importantly, these results were found in healthy older adults and in response to only a single administration of INDO.…”

Section: Discussionmentioning

confidence: 98%

“…Cyclo-oxygenase (COX) inhibitors are commonly used to treat pain and are associated with increased risk for cardiovascular events. Recently, it was reported in our laboratory that non-selective COX inhibition, via indomethacin (INDO), substantially altered large artery haemodynamics in older adults, whereas young adults appeared to be unaffected (Barnes 2012). However, central artery function is associated with, and affected by, concomitant changes in conduit and resistance vessel vasodilator capacity (Mitchell et al 2005;Kullo et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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The effect of ageing and indomethacin on forearm reactive hyperaemia in healthy adults

Taylor

Hines

Nicholson

et al. 2014

Experimental Physiology

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New Findings r What is the central question of this study?We aimed to investigate the effects of the cyclo-oxygenase (COX) inhibitor indomethacin on resistance vessel function in young and older adults and to test the hypothesis that indomethacin will attenuate forearm vascular conductance during reactive hyperaemia. r What is the main finding and its importance?Older adults demonstrated an attenuated vasodilator response to ischaemia after COX inhibition compared with their younger counterparts. This suggests that older adults do not compensate for the vascular changes induced by an acute dose of indomethacin. Long-term use of indomethacin may increase vascular resistance and reduce the response to acute haemodynamic stress in older adults. The risk for potential adverse cardiovascular consequences of COX inhibition should be considered.We have previously shown that non-selective cyclo-oxygenase inhibition, via indomethacin, unfavourably increased central blood pressure in older adults, with little effect in young adults. In addition, the vasoactive prostaglandins have been shown to contribute to both peripheral vasodilator responses and large artery function; however, there is little information available in older adults and conflicting reports in young adults on the extent to which resistance vessel function is influenced by indomethacin. Thus, we tested the hypothesis that cyclo-oxygenase inhibition using indomethacin would attenuate forearm vascular conductance during reactive hyperaemia in older adults compared with young adults. Forearm blood flow responses to 5 min of forearm ischaemia were measured in 26 healthy adults (13 young, 25 ± 5 years old; and 13 older, 65 ± 6 years old), using venous occlusion plethysmography before and after indomethacin. Baseline forearm blood flow and vascular conductance were not different between groups during either trial, and there were no age-related differences prior to cyclo-oxygenase inhibition. Peak forearm vascular conductance and blood flow were similar between groups before indomethacin, but lower in older adults after indomethacin compared with young adults (27 ± 4 versus 41 ± 4 ml (100 ml) −1 min −1 (100 mmHg) −1 , P = 0.02; and 23 ± 3 versus 33 ± 3 ml (100 ml) −1 min −1 , P = 0.02, respectively). These results, in conjunction with our previous findings in large arteries, suggest that ageing alters the effect of cyclo-oxygenase inhibition on vascular responses, and specifically, the resistance vessel responses underlying reactive hyperaemia.

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“…All measurements were performed by a trained medical doctor in duplicate, and the mean of these measurements was used in further analysis. Left ventricular wasted energy (E w ), which is the component of extra-myocardial O 2 requirement due to early systolic wave reflection, was estimated according to equation reported by Barnes et al (2012). AIx 75 was calculated as AIx adjusted for a HR of 75 beats min À1 .…”

Section: Assessment Of Arterial Stiffnessmentioning

confidence: 99%

The impact of consecutive freshwater trimix dives at altitude on human cardiovascular function

Lozo

Madden

Gunjaca

et al. 2014

Clin Physio Funct Imaging

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Self-contained underwater breathing apparatus (SCUBA) diving is regularly associated with numerous asymptomatic changes in cardiovascular function. Freshwater SCUBA diving presents unique challenges compared with open sea diving related to differences in water density and the potential for dive locations at altitude. The aim of this study was to evaluate the impact of freshwater trimix diving at altitude on human cardiovascular function. Ten divers performed two dives in consecutive days at 294 m altitude with the surface interval of 24 h. Both dives were at a depth of 45 m with total dive time 29 and 26 min for the first and second dive, respectively. Assessment of venous gas embolization, hydration status, cardiac function and arterial stiffness was performed. Production of venous gas emboli was low, and there were no significant differences between the dives. After the first dive, diastolic blood pressure was significantly reduced, which persisted up to 24 h. Left ventricular stroke volume decreased, and heart rate increased after both dives. Pulse wave velocity was unchanged following the dives. However, the central and peripheral augmentation index became more negative after both dives, indicating reduced wave reflection. Ejection duration and round trip travel time were prolonged 24 h after the first dive, suggesting longer-lasting suppression of cardiac and endothelial function. This study shows that freshwater trimix dives with conservative profiles and low venous gas bubble loads can result in multiple asymptomatic acute cardiovascular changes some of which were present up to 24 h after dive.

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Cyclooxygenase inhibition augments central blood pressure and aortic wave reflection in aging humans

Cited by 13 publications

References 48 publications

Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease

Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease

The effect of ageing and indomethacin on forearm reactive hyperaemia in healthy adults

The impact of consecutive freshwater trimix dives at altitude on human cardiovascular function

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