Prostaglandin synthesis blockade by ketoprofen attenuates respiratory and cardiovascular responses to static handgrip

Abstract

We investigated the effects of prostaglandin synthesis blockade on the changes in breathing pattern, mean blood pressure (MBP), and heart rate (HR) elicited by 3 min of static handgrip at 30% of the maximum voluntary contraction in 12 healthy volunteers. Before each handgrip trial, subjects were treated with intravenous administration of either saline placebo (control) or 1 mg/kg of ketoprofen. Muscle tension and integrated electromyographic activity of exercising muscles remained fairly constant during each trial. In agreement with our earlier findings, during control handgrip minute ventilation progressively increased (P < 0.01) due to a rise in tidal volume and, to a lesser extent, in respiratory frequency. Mean inspiratory flow, MBP, and HR also increased (P < 0.01). End-tidal PCO2 decreased (P < 0.05) during the late phases of control handgrip bouts. Ketoprofen administration reduced serum thromboxane B2 levels (from 57.5 +/- 7.0 to 1.6 +/- 0.4 pg/ml; P < 0.01) and significantly attenuated mean increases in minute ventilation (40.25 +/- 0.60%), tidal volume (37.78 +/- 7.48%), respiratory frequency (55.94 +/- 17.92%), inspiratory flow (42.66 +/- 5.11%), MBP (22.33 +/- 6.82%), and HR (11.04 +/- 2.75%) during the 3rd min of handgrip. End-tidal PCO2 remained close to normocapnic levels. In agreement with previous animal investigations, the present results show that arachidonic acid metabolites are involved in the regulation of the cardiovascular responses to static efforts in humans, possibly through a stimulatory action on muscle receptors. Furthermore, they provide the first experimental evidence that products of the cyclooxygenase metabolic pathway play a role in the mediation of the respiratory adjustments elicited by this form of exercise.

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

“…The majority of studies in healthy humans have shown that inhibiting exercise-induced prostanoid synthesis attenuates reflex cardiovascular responses (7,8,14,23,25). These studies all used handgrip exercise, and they all administered either indomethacin or ketoprofen.…”

“…The standard of care Rating of perceived exertion 0.5 kg 7 (6-9) 6 (6-9) 6 (6-7) 6 (6-7) 1.0 kg 9 (6-11) 8 (6-10) 7 (6-9) 7 (6-7) 1.5 kg 10 (8-13) 9 (8-13)* 8 (6-11) 7 (6-9) 2.0 kg 11 (9)(10)(11)(12)(13)(14) 10 (9-14)* 9 (7-12) 9 (7-10) 7.0 kg 15 (13)(14)(15)(16)(17) Data are shown as medians with ranges in parentheses; n ϭ 7 PAD patients and 7 healthy control subjects. *Significant difference between groups at the specific time point.…”

“…A different study (36) in cats showed that intravenous indomethacin attenuated the rise in MAP in response to static hindlimb contraction. Many studies (7,8,14,23,25) in healthy humans have demonstrated that blocking the prostanoid pathway attenuates reflex cardiovascular responses to exercise, although two studies (9, 12) have contradicted these findings. Currently, it is believed that prostanoids are especially important for sensitizing group III afferents during low-intensity dynamic exercise (i.e., before the onset of muscle metaboreflex activation).…”

Prostaglandin synthesis can be inhibited locally by infusion of NSAIDS through microdialysis catheters in human skeletal muscle

“…Compared with intra-arterial or intravenous infusions (4,11,15), local injections and oral intake of pharmacological substances (1), the presently used microdialysis technique with continuous infusion of NSAIDs allows for both a graded blockade as well as for maintaining steady-state situations over a long time period. In the present study an almost constant block was maintained from the end of exercise until 3 h postexercise (shown in Fig.…”

Skeletal Muscle Reflex in Heart Failure Patients

“…4 The triggering mediators responsible for the ergoreflex stimulation and their involvement in the abnormal exercise responses in CHF remain to be established. Different metabolic and humoral products have been studied in animals [7][8][9][10][11][12] and in humans, [13][14][15] but few investigators have investigated factors specifically involved in the ergoreflex overactivation of CHF patients. 16,17 One (or more) of these mediators may be involved as a link between alterations in muscle metabolism and/or hemodynamics present in CHF and the ventilatory response to exercise, via activation of muscle reflex.…”