Agonist-dependent variablity of contributions of nitric oxide and prostaglandins in human skeletal muscle

William G. Schrage, Niki M. Dietz, John H. Eisenach, Michael Joseph Joyner

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The relative contributions of endothelium-dependent dilators [nitric oxide (NO), prostaglandins (PGs), and endothelium-derived hyperpolarizing factor (EDHF)] in human limbs are poorly understood. We tested the hypothesis that relative contributions of NO and PGs differ between endothelial agonists acetylcholine (ACh; 1, 2, and 4 μg·dl-1·min -1) and bradykinin (BK; 6.25, 25, and 50 ng·dl- 1·min-1). We measured forearm blood flow (FBF) using venous occlusion plethysmography in 50 healthy volunteers (27 ± 1 yr) in response to brachial artery infusion of ACh or BK in the absence and presence of inhibitors of NO synthase [NOS; with NG-monomethyl-L-arginine (L-NMMA)] and cyclooxygenase (COX; with ketorolac). Furthermore, we tested the idea that the NOS + COX-independent dilation (in the presence of L-NMMA + ketorolac, presumably EDHF) could be inhibited by exogenous NO administration, as reported in animal studies. FBF-increased ∼10-fold in the ACh control; L-NMMA reduced baseline FBF and ACh dilation, whereas addition of ketorolac had no further effect. Ketorolac alone did not alter ACh dilation, but addition of L-NMMA reduced ACh dilation significantly. For BK infusion, FBF increased ∼10-fold in the control condition; L-NMMA tended to reduce BK dilation (P < 0.1), and addition of ketorolac significantly reduced BK dilation. Similar to ACh, ketorolac alone did not alter BK dilation, but addition of L-NMMA reduced BK dilation. To test the idea that NO can inhibit the NOS + COX-independent portion of dilation, we infused a dose of sodium nitroprusside (NO-clamp technique) during ACh or BK that restored the reduction in baseline blood flow due to L-NMMA. Regardless of treatment order, the NO clamp restored baseline FBF but did not reduce the NOS + COX-independent dilation to ACh or BK. We conclude that the contribution of NO and PGs differs between ACh and BK, with ACh being more dependent on NO and BK being mostly dependent on a NOS + COX-independent mechanism (EDHF) in healthy young adults. The NOS + COX-independent dilation does not appear sensitive to feedback inhibition from NO in the human forearm.

Original languageEnglish (US)
Pages (from-to)1251-1257
Number of pages7
JournalJournal of Applied Physiology
Volume98
Issue number4
DOIs
StatePublished - Apr 2005

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omega-N-Methylarginine
Prostaglandins
Dilatation
Nitric Oxide
Skeletal Muscle
Ketorolac
Forearm
Endothelium
Cholinergic Agonists
Plethysmography
Brachial Artery
Nitroprusside
Bradykinin
Prostaglandin-Endoperoxide Synthases
Nitric Oxide Synthase
Young Adult
Healthy Volunteers
Extremities

Keywords

  • Brachial artery
  • Cyclooxygenase
  • Human endothelium
  • Intra-arterial infusion

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Agonist-dependent variablity of contributions of nitric oxide and prostaglandins in human skeletal muscle. / Schrage, William G.; Dietz, Niki M.; Eisenach, John H.; Joyner, Michael Joseph.

In: Journal of Applied Physiology, Vol. 98, No. 4, 04.2005, p. 1251-1257.

Research output: Contribution to journalArticle

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