Endothelium-dependent blunting of myogenic responsiveness after chronic hypoxia.
Blunted agonist-induced vasoconstriction after chronic hypoxia is associated with endothelium-dependent vascular smooth muscle (VSM) cell hyperpolarization and decreased vessel-wall Ca(2+) concentration ([Ca(2+)]). We hypothesized that myogenic vasoconstriction and pressure-induced Ca(2+) influx would also be attenuated in vessels from chronically hypoxic (CH) rats. Mesenteric resistance arteries isolated from CH [barometric pressure (BP), 380 Torr for 48 h] or normoxic control (BP, 630 Torr) rats were cannulated and pressurized. VSM cell resting membrane potential was recorded at intraluminal pressures of 40-120 Torr under normoxic conditions. VSM cells in vessels from CH rats were hyperpolarized compared with control rats at all pressures. Inner diameter was maintained for vessels from control rats, whereas vessels from CH rats developed less tone as pressure was increased. Pressure-induced increases in vessel-wall [Ca(2+)] were also attenuated for arteries from CH rats. Endothelium removal restored myogenic constriction to vessels from CH rats and normalized VSM cell resting membrane potential and pressure-induced Ca(2+) responses to control levels. Myogenic constriction and pressure-induced vessel-wall [Ca(2+)] increases remained blunted in the presence of nitric oxide (NO) synthase inhibition for arteries from CH rats. We conclude that blunted myogenic reactivity after chronic hypoxia results from a non-NO, endothelium-dependent VSM cell hyperpolarizing influence.
Earley
Scott
S
Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque 87131-5218, USA. searley@unm.edu
Walker
Benjimen R
BR
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D001273:Atmosphere Exposure Chambers; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008643:Mesentery / Q000098:blood supply; D009129:Muscle Tonus / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014654:Vascular Patency / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D002118:Calcium