Chronic intermittent hypoxia alters NE reactivity and mechanics of skeletal muscle resistance arteries.
Although arterial dilator reactivity is severely impaired during exposure of animals to chronic intermittent hypoxia (CIH), few studies have characterized vasoconstrictor responsiveness in resistance arteries of this model of sleep-disordered breathing. Sprague-Dawley rats were exposed to CIH (10% inspired O2 fraction for 1 min at 4-min intervals; 12 h/day) for 14 days. Control rats were housed under normoxic conditions. Diameters of isolated gracilis muscle resistance arteries (GA; 120-150 microm) were measured by television microscopy before and during exposure to norepinephrine (NE) and angiotensin II (ANG II) and at various intraluminal pressures between 20 and 140 mmHg in normal and Ca2+-free physiological salt solution. There was no difference in the ability of GA to constrict in response to ANG II (P = 0.42; not significant; 10(-10)-10(-7) M). However, resting tone, myogenic activation, and vasoconstrictor responses to NE (P < 0.001; 10(-9)-10(-6) M) were reduced in CIH vs. controls. Treatment of rats with the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol; 1 mM) in the drinking water restored myogenic responses and NE-induced constrictions of CIH rats, suggesting that elevated superoxide production during exposure to CIH attenuates vasoconstrictor responsiveness to NE and myogenic activation in skeletal muscle resistance arteries. CIH also leads to an increased stiffness and reduced vessel wall distensibility that were not correctable with oral tempol treatment.
Phillips
Shane A
SA
Department of Physiology, Medical College of Wisconsin, Milwaukee, USA.
Olson
E B
EB
Lombard
Julian H
JH
Morgan
Barbara J
BJ
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D003187:Compliance; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D000860:Hypoxia; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D014655:Vascular Resistance; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D010100:Oxygen; C001803:tempol; D009638:Norepinephrine