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.

[1]  S. Earley,et al.  48-h Hypoxic exposure results in endothelium-dependent systemic vascular smooth muscle cell hyperpolarization. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[2]  F. Edwards,et al.  Intercellular electrical communication among smooth muscle and endothelial cells in guinea‐pig mesenteric arterioles , 2001, The Journal of physiology.

[3]  B. Walker,et al.  Correlation of HO-1 expression with onset and reversal of hypoxia-induced vasoconstrictor hyporeactivity. , 2001, American journal of physiology. Heart and circulatory physiology.

[4]  B. Walker,et al.  Renal vasodilatory influence of endogenous carbon monoxide in chronically hypoxic rats. , 2000, American journal of physiology. Heart and circulatory physiology.

[5]  G. G. Emerson,et al.  Electrical Coupling Between Endothelial Cells and Smooth Muscle Cells in Hamster Feed Arteries: Role in Vasomotor Control , 2000, Circulation research.

[6]  W. Jackson.  Hypoxia Does Not Activate ATP‐Sensitive K+ Channels in Arteriolar Muscle Cells , 2000, Microcirculation.

[7]  C. Hill,et al.  Incidence of myoendothelial gap junctions in the proximal and distal mesenteric arteries of the rat is suggestive of a role in endothelium-derived hyperpolarizing factor-mediated responses. , 2000, Circulation research.

[8]  B. Walker,et al.  Role of endothelial carbon monoxide in attenuated vasoreactivity following chronic hypoxia. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[9]  M. Ward,et al.  Impaired reactivity of rat aorta to phenylephrine and KCl after prolonged hypoxia: role of the endothelium. , 1998, Journal of applied physiology.

[10]  M. Nelson,et al.  Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure , 1998, The Journal of physiology.

[11]  S. Silberberg,et al.  Voltage‐induced slow activation and deactivation of mechanosensitive channels in Xenopus oocytes , 1997, The Journal of physiology.

[12]  M. Ward,et al.  Hyporeactivity of rat diaphragmatic arterioles after exposure to hypoxia in vivo. Role of the endothelium. , 1997, American journal of respiratory and critical care medicine.

[13]  M. Mulvany,et al.  KCa-channel blockade prevents sustained pressure-induced depolarization in rat mesenteric small arteries. , 1997, The American journal of physiology.

[14]  L. Zhang,et al.  Chronic hypoxia suppresses pharmacomechanical coupling of the uterine artery in near‐term pregnant sheep. , 1997, The Journal of physiology.

[15]  G. Semenza,et al.  Hypoxia-inducible Factor-1 Mediates Transcriptional Activation of the Heme Oxygenase-1 Gene in Response to Hypoxia* , 1997, The Journal of Biological Chemistry.

[16]  G. Meininger,et al.  Calcium entry and myogenic phenomena in skeletal muscle arterioles. , 1994, The American journal of physiology.

[17]  M. J. Davis,et al.  Stretch-activated single-channel and whole cell currents in vascular smooth muscle cells. , 1992, The American journal of physiology.

[18]  B. Walker,et al.  Attentuation of systemic vasoreactivity in chronically hypoxic rats. , 1991, The American journal of physiology.

[19]  B. Duling,et al.  Ca2+ sensitivity of isolated arterioles from the hamster cheek pouch. , 1991, The American journal of physiology.

[20]  J. Bevan,et al.  Stretch of vascular smooth muscle activates tone and 45Ca2+ influx. , 1989, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[21]  N. Standen,et al.  Noradrenaline contracts arteries by activating voltage-dependent calcium channels , 1988, Nature.

[22]  M. Nelson,et al.  Single nisoldipine-sensitive calcium channels in smooth muscle cells isolated from rabbit mesenteric artery. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[23]  D. Harder.  Pressure‐Dependent Membrane Depolarization in Cat Middle Cerebral Artery , 1984, Circulation research.

[24]  H. Suzuki,et al.  Effects of sodium nitroprusside on smooth muscle cells of rabbit pulmonary artery and portal vein. , 1978, The Journal of pharmacology and experimental therapeutics.

[25]  B. Walker,et al.  Role of CO in attenuated vasoconstrictor reactivity of mesenteric resistance arteries after chronic hypoxia. , 2002, American journal of physiology. Heart and circulatory physiology.

[26]  D. Heistad,et al.  Regulation of the cerebral circulation: role of endothelium and potassium channels. , 1998, Physiological reviews.

[27]  Lubo Zhang,et al.  Effects of chronic hypoxia on Ca2+ mobilization and Ca2+ sensitivity of myofilaments in uterine arteries. , 1998, American journal of physiology. Heart and circulatory physiology.