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

Abstract

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 ...

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

“…In general, changes in arterial oxygen content evoke either increases (hypoxia) or decreases (hyperoxia) in blood flow with the net effect of maintaining constant oxygen delivery to the contracting muscles (73, 80 -83, 182, 399, 504, 509, 510). A similar compensatory vasodilator response is seen when oxygen delivery is reduced by lowering perfusion pressure via balloon inflation to the contracting muscles (74,75,(77)(78)(79).…”

“…However, a combination of downstream vasodilation and collateral circulation around the elbow permitted the blood flow responses to submaximal forearm exercise to recover rapidly (FIGURE 12). At steady state, they were remarkably normal (74,75,78,79,85).…”

Roles of nitric oxide and prostaglandins in the hyperemic response to a maximal metabolic stimulus: redundancy prevails

“…In the same light, it was noted by Schrage et al (2004) that both NO and PGs contribute to exercise hyperemic responses independently, with some emphasis on a larger role for NO as compared to PGs. In a model using partial intra-arterial ischemia during exercise, NO synthase inhibition was noted to blunt vasodilatory responses, however this response was noted to be independent of PGs Casey and Joyner 2011). Naylor et al (1999) compared ischemia alone and ischemic exercise hyperemic responses with and without systemic prostaglandin blockade using indomethacin and ibuprofen.…”

“…A review of the repeatability data for this ischemic exercise model showed a trend of increasing baseline blood flow for each successive trial that may have masked effects of drug infusion on baseline flow (Lopez et al 2012). This was despite evidence from Doppler ultrasound studies using beat-to-beat blood velocity measures that a 20-min resting period was adequate for blood flow to return to baseline following handgrip exercise (Casey and Joyner 2011). The use of VOP and thus postexperiment data analysis precluded the ability to ensure a complete return to baseline after resting periods.…”

Characteristics and effectiveness of vasodilatory and pressor compensation for reduced relaxation time during rhythmic forearm contractions

“…Hypoperfusion models (Casey & Joyner, 2009b, 2011b have demonstrated that compensatory vasodilatation during moderate intensity exercise is mediated in part by NO (ß20%; Casey & Joyner, 2009a) and adenosine (ß19%; Casey & Joyner, 2011a), whereas prostaglandins are not obligatory (Casey & Joyner, 2011c). The red blood cell acting as an oxygen sensor would appear to be a prime candidate for compensatory vasodilatation given the impairment to flow at a fixed metabolic demand (Dietrich et al 2000;Ellsworth, 2000;González-Alonso, 2012).…”