TY - JOUR
T1 - Integration of hypoxic dilation signaling pathways for skeletal muscle resistance arteries
AU - Frisbee, Jefferson C.
AU - Maier, Kristopher G.
AU - Falck, J R
AU - Roman, Richard J.
AU - Lombard, Julian H.
PY - 2002
Y1 - 2002
N2 - 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 KCa channels. When only COX pathways were intact, responses to moderate-severe hypoxia were largely retained (79% of normal) mediated via KATP channels. Vessel responses to moderate hypoxia were retained with only 20-HETE systems intact mediated via KCa 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-PGF1α 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), PGI2 production (severe hypoxia), and reduced 20-HETE levels (moderate hypoxia).
AB - 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 KCa channels. When only COX pathways were intact, responses to moderate-severe hypoxia were largely retained (79% of normal) mediated via KATP channels. Vessel responses to moderate hypoxia were retained with only 20-HETE systems intact mediated via KCa 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-PGF1α 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), PGI2 production (severe hypoxia), and reduced 20-HETE levels (moderate hypoxia).
KW - 20-hydroxyeicosatetraenoic acid
KW - Cytochrome P-450 4a enzymes
KW - Microvessels
KW - Nitric oxide
KW - Oxygen-induced vascular reactivity
KW - Prostacyclin
KW - Skeletal muscle microcirculation
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U2 - 10.1152/ajpregu.00741.2001
DO - 10.1152/ajpregu.00741.2001
M3 - Article
C2 - 12121842
AN - SCOPUS:0036337214
SN - 0363-6119
VL - 283
SP - R309-R319
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 2 52-2
ER -