PROSTAGLANDIN SYNTHESIS BLOCKADE BY KETOPROFEN ATTENUATES RESPIRATORYAND CARDIOVASCULAR-RESPONSES TO STATIC HANDGRIP

We investigated the effects of prostaglandin synthesis blockade on the changes in breathing pattern, mean blood pressure (MBP), and heart ra te (HR) elicited by 3 min of static handgrip at 30% of the maximum vol untary contraction in 12 healthy volunteers. Before each handgrip tria l, subjects were treated with intravenous administration of either sal ine placebo (control) or 1 mg/kg of ketoprofen. Muscle tension and int egrated electromyographic activity of exercising muscles remained fair ly 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 res piratory 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 th romboxane B-2 levels (from 57.5 +/- 7.0 to 1.6 +/- 0.4 pg/ml; P < 0.01 ) and significantly attenuated mean increases in minute ventilation (4 0.25 +/- 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 pr evious animal investigations, the present results show that arachidoni c acid metabolites are involved in the regulation of the cardiovascula r responses to static efforts in humans, possibly through a stimulator y action on muscle receptors. Furthermore, they provide the first expe rimental evidence that products of the cyclooxygenase metabolic pathwa y play a role in the mediation of the respiratory adjustments elicited by this form of exercise.