Integration of hypoxic dilation signaling pathways for skeletal muscle resistance arteries. Am J Physiol Regul Integr Comp Physiol 2002 Aug;283(2):R309-19
Date
07/18/2002Pubmed ID
12121842DOI
10.1152/ajpregu.00741.2001Scopus ID
2-s2.0-0036337214 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
Mediator contributions to hypoxic dilation of rat gracilis muscle resistance arteries were determined by measuring dilation, vascular smooth muscle hyperpolarization, and metabolite production after incremental hypoxia. Nitric oxide (NO) synthase inhibition abolished responses to mild hypoxia, whereas COX inhibition impaired responses to more severe hypoxia by 77%. Blocking 20-hydroxyeicosatetraenoic acid (20-HETE) impaired responses to moderate hypoxia. With only NO systems intact, responses were maintained with mild hypoxia (88% normal) mediated via K(Ca) channels. When only COX pathways were intact, responses to moderate-severe hypoxia were largely retained (79% of normal) mediated via K(ATP) channels. Vessel responses to moderate hypoxia were retained with only 20-HETE systems intact mediated via K(Ca) channels. NO production increased 5.6-fold with mild hypoxia; greater hypoxia was without further effect. With increased hypoxia, 20-HETE levels fell to 40% of control values. 6-keto-PGF(1alpha) levels were not altered with mild hypoxia, but increased 4.6-fold with severe hypoxia. These results suggest vascular reactivity to progressive hypoxia represents an integration of NO production (mild hypoxia), PGI(2) production (severe hypoxia), and reduced 20-HETE levels (moderate hypoxia).
Author List
Frisbee JC, Maier KG, Falck JR, Roman RJ, Lombard JHMESH terms used to index this publication - Major topics in bold
6-Ketoprostaglandin F1 alphaAnimals
Arteries
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Epoprostenol
Hydroxyeicosatetraenoic Acids
Hypoxia
In Vitro Techniques
Male
Muscle, Skeletal
Nitric Oxide
Nitric Oxide Synthase
Potassium Channel Blockers
Potassium Channels
Rats
Rats, Sprague-Dawley
Signal Transduction
Vascular Resistance
Vasodilation
