title: Roles of nitric oxide and prostaglandins in the hyperemic response to a maximal metabolic stimulus: redundancy prevails.
abstract: Vasodilatory mechanisms controlling post-exercise or post-ischemic hyperemia are thought to be under redundant control and remain incompletely understood. A maximal metabolic stimulus evoked by ischemic exercise (IE) might limit redundancy by full activation of multiple pathways. We tested whether nitric oxide (NO) and/or prostaglandins contribute to the hyperemic response to IE. 17 subjects were randomized into two groups and performed three trials of IE during control (saline), N (G)-monomethyl-L-arginine (L-NMMA; NOS inhibition) (protocol 1) or ketorolac (cyclooxygenase inhibition) infusion (protocol 2), and combined L-NMMA/ketorolac infusion via a brachial arterial catheter. Forearm blood flow (FBF) was measured with venous occlusion plethysmography following IE trials consisting of 5 min of ischemia and simultaneous rhythmic handgrip exercise (final 2 min). Peak and total (area under the curve) FBF and blood pressure (MAP) were measured for 3 min after each trial. Forearm vascular conductance (FVC) was calculated as FBF/MAP. Change (Δ) in peak FBF and FVC from baseline differed only between peak FBF for the saline and L-NMMA + ketorolac trials in protocol 1. Peak ΔFBF was 26.8 ± 2.5, 30.0 ± 2.8, and 33.9 ± 3.6 ml 100 ml(-1) min(-1) for saline, L-NMMA, and L-NMMA + ketorolac trials (P = 0.04). For protocol 1 (n = 8), total ΔFVC was 59.6 ± 4.3, 57.8 ± 6.0, and 59.9 ± 5.6 ml 100 ml(-1) 100 mmHg(-1) for saline, L-NMMA, and L-NMMA + ketorolac trials, (P = 0.82). For protocol 2 (n = 9), total ΔFVC was 54.2 ± 5.0, 56.9 ± 4.5, and 56.5 ± 5.3 ml 100 ml(-1) 100 mmHg(-1) for saline, ketorolac, and ketorolac + L-NMMA trials, (P = 0.69). These results suggest that NO and PGs are not obligatory for the hyperemic response to IE, and other vasodilator mechanisms predominate.
authors.affiliation: Department of Anesthesiology, Vanderbilt University School of Medicine, 1161 21st Avenue, Nashville, TN 37232, USA. mglopez3@gmail.com
authors.forename: Marcos G
authors.initials: MG
authors.lastname: Lopez
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Silva
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Joyner
authors.forename: Darren P
authors.initials: DP
authors.lastname: Casey
mesh_terms: D001794:Blood Pressure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015444:Exercise / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D018737:Hand Strength; D006801:Humans; D006940:Hyperemia / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism; D020910:Ketorolac / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011453:Prostaglandins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D020910:Ketorolac