title: Impact of combined NO and PG blockade on rapid vasodilation in a forearm mild-to-moderate exercise transition in humans.
abstract: We tested the hypothesis that nitric oxide (NO) and prostaglandins (PGs) contribute to the rapid vasodilation that accompanies a transition from mild to moderate exercise. Nine healthy volunteers (2 women and 7 men) lay supine with forearm at heart level. Subjects were instrumented for continuous brachial artery infusion of saline (control condition) or combined infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) and ketorolac (drug condition) to inhibit NO synthase and cyclooxygenase, respectively. A step increase from 5 min of steady-state mild (5.4 kg) rhythmic, dynamic forearm handgrip exercise (1 s of contraction followed by 2 s of relaxation) to moderate (10.9 kg) exercise for 30 s was performed. Steady-state forearm blood flow (FBF; Doppler ultrasound) and forearm vascular conductance (FVC) were attenuated in drug compared with saline (control) treatment: FBF = 196.8 +/- 30.8 vs. 281.4 +/- 34.3 ml/min and FVC = 179.3 +/- 29.4 vs. 277.8 +/- 34.8 ml.min(-1).100 mmHg(-1) (both P < 0.01). FBF and FVC increased from steady state after release of the initial contraction at the higher workload in saline and drug conditions: DeltaFBF = 72.4 +/- 8.7 and 52.9 +/- 7.8 ml/min, respectively, and DeltaFVC = 66.3 +/- 7.3 and 44.1 +/- 7.0 ml.min(-1).100 mmHg(-1), respectively (all P < 0.05). The percent DeltaFBF and DeltaFVC were not different during saline infusion or combined inhibition of NO and PGs: DeltaFBF = 27.2 +/- 3.1 and 28.1 +/- 3.8%, respectively (P = 0.78) and DeltaFVC = 25.7 +/- 3.2 and 26.0 +/- 4.0%, respectively (P = 0.94). The data suggest that NO and vasodilatory PGs are not obligatory for rapid vasodilation at the onset of a step increase from mild- to moderate-intensity forearm exercise. Additional vasodilatory mechanisms not dependent on NO and PG release contribute to the immediate and early increase in blood flow in an exercise-to-exercise transition.
authors.affiliation: School of Physical and Health Education, Queen's University, 69 Union St., Kingston, Ontario, Canada K7L 3N6.
authors.forename: Natasha R
authors.initials: NR
authors.lastname: Saunders
authors.forename: Frank A
authors.initials: FA
authors.lastname: Dinenno
authors.forename: Kyra E
authors.initials: KE
authors.lastname: Pyke
authors.forename: Anna M
authors.initials: AM
authors.lastname: Rogers
authors.forename: Michael E
authors.initials: ME
authors.lastname: Tschakovsky
mesh_terms: D000328:Adult; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015444:Exercise / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D020910:Ketorolac / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D011448:Prostaglandin Antagonists; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester; D020910:Ketorolac