Mechanism of physiological hypoxia-induced depression of vascular smooth muscle contraction

Detar, R

doi:10.1152/ajpheart.1980.238.6.h761

Cited by 37 publications

(40 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cellular respiration is generally thought to be independent of oxygen tension at levels that cause vasodilation (i.e., PO 2 values between 70 and 10 mmHg), because cytochrome oxidase is saturated with oxygen at these partial pressures (e.g., 46). Also, levels of oxygen that cause vasodilation do not cause large changes in intracellular ATP or ADP concentration in vascular tissue (e.g., 6,10,25,28). However, the PO 2 at the level of the enzymes of the mitochondrial respiratory chain is unknown, although it will presumably be less than that in the bulk extracellular space due to diffusion gradients.…”

Section: Discussionmentioning

confidence: 99%

Effects of hypoxia, anoxia, and metabolic inhibitors on K_ATP channels in rat femoral artery myocytes

Quayle¹,

Turner²,

Burrell³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Effects of hypoxia, anoxia, and metabolic inhibitors on KATP channels in rat femoral artery myocytes. Am J Physiol Heart Circ Physiol 291: H71-H80, 2006. First published February 17, 2006 doi:10.1152/ajpheart.01107.2005.-Vascular ATP-sensitive potassium (KATP) channels have an important role in hypoxic vasodilation. Because KATP channel activity depends on intracellular nucleotide concentration, one hypothesis is that hypoxia activates channels by reducing cellular ATP production. However, this has not been rigorously tested. In this study we measured K ATP current in response to hypoxia and modulators of cellular metabolism in single smooth muscle cells from the rat femoral artery by using the whole cell patch-clamp technique. KATP current was not activated by exposure of cells to hypoxic solutions (PO2 ϳ35 mmHg). In contrast, voltagedependent calcium current and the depolarization-induced rise in intracellular calcium concentration ([Ca 2ϩ ]i) was inhibited by hypoxia. Blocking mitochondrial ATP production by using the ATP synthase inhibitor oligomycin B (3 M) did not activate current. Blocking glycolytic ATP production by using 2-deoxy-D-glucose (5 mM) also did not activate current. The protonophore carbonyl cyanide m-chlorophenylhydrazone (1 M) depolarized the mitochondrial membrane potential and activated K ATP current. This activation was reversed by oligomycin B, suggesting it occurred as a consequence of mitochondrial ATP consumption by ATP synthase working in reverse mode. Finally, anoxia induced by dithionite (0.5 mM) also depolarized the mitochondrial membrane potential and activated K ATP current. Our data show that: 1) anoxia but not hypoxia activates KATP current in femoral artery myocytes; and 2) inhibition of cellular energy production is insufficient to activate K ATP current and that energy consumption is required for current activation. These results suggest that vascular K ATP channels are not activated during hypoxia via changes in cell metabolism. Furthermore, part of the relaxant effect of hypoxia on rat femoral artery may be mediated by changes in [Ca 2ϩ ]i through modulation of calcium channel activity. smooth muscle; ion channels; potassium channels ATP-SENSITIVE POTASSIUM (K ATP ) channels are involved in the hypoxic vasodilation that couples blood flow to metabolic demand, for example, in the coronary (44), skeletal muscle (30), and cerebral circulations (42). Hypoxia is thought to activate K ATP channels either by acting directly on the smooth muscle cells or by causing release of vasodilator metabolites from surrounding tissue or endothelial cells, which in turn activates channels via receptor-coupled signal transduction pathways (e.g., 9, 23, 30, 37, 43, 44). K ATP channels are regulated by intracellular ATP and ADP, and the direct vasodilator action of hypoxia may therefore occur as a consequence of hypoxia changing intracellular nucleotide levels in arterial myocytes (9, 27, 44). Alternatively, oxygen tension regulates the activity of some channels independently of changes i...

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of hypoxia, anoxia, and metabolic inhibitors on K_ATP channels in rat femoral artery myocytes

Quayle¹,

Turner²,

Burrell³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Because all responses to hypoxia were obtained under condit ions of complet e membrane depolarization , it is doubtful that differences in the effects of hypoxia on membrane hyperpolarization (16,17) could have contributed to the observed age-related differences in response to hypoxia. Similarly, it is doubtful that hypoxia-induced changes in sodiumcalcium exchange (18) were involved since extracellular sodium concentration during hypoxia was too low to support this mechanism (19). It remains possible, however, that other factors suggested to playa role in hypoxic relaxation, such as release of a relaxing factor from the vascular endothelium (20), inhibition ofcalcium uptake (21,22), stimulation of calcium extrusion (23,24), or changes in anaerobic glycolytic capacity (25,26) may be involved in the changing sensitivity to hypoxia which occurs with age.…”

Section: Discussionmentioning

confidence: 99%

Developmental Changes in Thickness, Contractility, and Hypoxic Sensitivity of Newborn Lamb Cerebral Arteries

Pearce

Ashwal

1987

Pediatr Res

View full text Add to dashboard Cite

[S.A.j ischemia, edema, and infarction. Concomitant elevations in arterial carbon dioxide tension and compensatory increases in blood pressure may acutely increase cerebral blood flow, but these changes can also contribute to the development of subependymal or intraventricular hemorrhage ( I, 2), particularly upon reoxygenation. Such pathophysiological changes demonstrate that regulation of cerebral perfusion in the newborn is impaired by hypoxia (3). The reasons for this impairment, however, remain unclear.The vulnerability of the newborn cerebral circulation to hypoxic damage may be due to age-related differences in vascular structure and function. In newborn vessels, wall thickness and tension-generating capacity are decreased relative to corresponding adult vessels (4). Adrenergic innervation and recepto r sensitivity are also decreased (5, 6). These differences are of importance not only at the microcirculatory level, but also in the large cerebral arteries which, in the adult , can contribute up to 50% of total cerebrovascular resistance (7). Thus, newborn vessels may not be able to adjust with the speed and force required to maintain cerebral perfusion during hypoxia, or to limit cerebral perfusion during reoxygenation. To explore this hypothesis, we examined the rates and magnitudes of relaxation during hypoxia in carotid and cerebral arteries isolated from newborn lambs and adult sheep. Vessel thicknesses and normoxic force developm ent were also examined and compared. We paid particular attention to the differences between carotid and cerebral arteries, and to the effects of maturation on these differences. METHODSSegments of rostral choroidal, posterior communicating, basilar, and common carotid arteries were obtained from 3-to 7-day-old lambs and adult sheep and studied using standard in vitro techniques (5, 8). Each segment was cut to a length of 5 mm , cannulated with mou nting wires, and suspended between a Grass IT.03 force transducer and a post attached to a microm eter used to control resting tension. The segments were equilibrated in a bicarbonate Krebs solution containing (in mM/liter): NaCI 122, NaHC03 25.6, dextrose 5.56, KCl5.17, MgS0 4 2.49, CaCh 1.60, ascorbic acid 0.114, and disodium EDTA 0.027. During equilibration, the vessel segments were stretched to obtain optimal resting tensions of 0.5 to 1.0 g for the cerebral and carotid artery segments. Optimal values of resting tension were determined in preliminary length-tension studies. Unl ess otherwise specified, the vessels were continuously bubbled with 95% Os, 5% CO2 and maintained at normal body temperature.Each vessel segment was contracted three times in succession by exposure to an isotonic Krebs solution containing 120 mM KCl and 5.2 mM NaC!. Each contraction lasted 24 min , with a 30-min rest period in normal Krebs allowed between consecuti ve 192ABSTRACf. The present studies were conducted to examine the possibility that the increased vulnerability of the newborn brain to hypoxia may be due to age-related differences in vas...

show abstract

“…We conclude that endothelial derived CO accounts for persistent VSM cell hyperpolarization and vasoconstrictor hyporeactivity after CH. rat; carbon monoxide; calcium imaging; vasoreactivity CHRONIC HYPOXIC EXPOSURE RESULTS in blunted systemic vasoconstrictor responses in conscious rats (6) that persists upon restoration of normoxia (11), which demonstrates that the consequences of chronic hypoxia (CH) are distinct from acute responses to this stimulus (5). Persistently blunted vasoconstriction after CH has been observed in response to both receptor-dependent (6,10) and receptor-independent stimuli (23).…”

mentioning

confidence: 99%

48-h Hypoxic exposure results in endothelium-dependent systemic vascular smooth muscle cell hyperpolarization

Earley

Naik

Walker

2002

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Earley, Scott, Jay S. Naik, and Benjimen R. Walker. 48-h Hypoxic exposure results in endothelium-dependent systemic vascular smooth muscle cell hyperpolarization. Am J Physiol Regulatory Integrative Comp Physiol 283: R79-R85, 2002. First published March 22, 2002 10.1152/ ajpregu.00104.2002 results in reduced sensitivity to vasoconstrictors in conscious rats that persists upon restoration of normoxia. We hypothesized that this effect is due to endothelium-dependent hyperpolarization of vascular smooth muscle (VSM) cells after CH. VSM cell resting membrane potential was determined for superior mesenteric artery strips isolated from CH rats (PB ϭ 380 Torr for 48 h) and normoxic controls. VSM cells from CH rats studied under normoxia were hyperpolarized compared with controls. Resting vessel wall intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) and pressure-induced vasoconstriction were reduced in vessels isolated from CH rats compared with controls. Vasoconstriction and increases in vessel wall [Ca 2ϩ ]i in response to the ␣1-adrenergic agonist phenylephrine (PE) were also blunted in resistance arteries from CH rats. Removal of the endothelium normalized resting membrane potential, resting vessel wall [Ca 2ϩ ]i, pressure-induced vasoconstrictor responses, and PE-induced constrictor and Ca 2ϩ responses between groups. Whereas VSM cell hyperpolarization persisted in the presence of nitric oxide synthase inhibition, heme oxygenase inhibition restored VSM cell resting membrane potential in vessels from CH rats to control levels. We conclude that endothelial derived CO accounts for persistent VSM cell hyperpolarization and vasoconstrictor hyporeactivity after CH. rat; carbon monoxide; calcium imaging; vasoreactivity CHRONIC HYPOXIC EXPOSURE RESULTS in blunted systemic vasoconstrictor responses in conscious rats (6) that persists upon restoration of normoxia (11), which demonstrates that the consequences of chronic hypoxia (CH) are distinct from acute responses to this stimulus (5). Persistently blunted vasoconstriction after CH has been observed in response to both receptor-dependent (6, 10) and receptor-independent stimuli (23). Studies demonstrating blunted vasoreactivity following CH in isolated vessel preparations such as aortic (2, 4) and uterine artery rings (10, 25) as well as isolated diaphragmatic resistance arteries (23) suggest that this effect is an inherent vascular property and is not mediated by circulating factors or by altered sympathetic nervous system activity. Interestingly, chronic obstructive pulmonary disease patients exhibit chronic vasodilation of the forearm circulation that is proportional to the degree of hypoxemia present (3), which suggests that attenuated vasoconstriction may be associated with this pathology.Ionic conductances regulate the contractile state and reactivity of blood vessels. For example, voltage-dependent Ca 2ϩ channels (VDCCs) account for a significant portion of Ca 2ϩ influx into vascular smooth muscle (VSM) cells (8). VSM resting membrane potential (RMP) largely dete...

show abstract

Mechanism of physiological hypoxia-induced depression of vascular smooth muscle contraction

Cited by 37 publications

References 0 publications

Effects of hypoxia, anoxia, and metabolic inhibitors on K_ATP channels in rat femoral artery myocytes

Effects of hypoxia, anoxia, and metabolic inhibitors on K_ATP channels in rat femoral artery myocytes

Developmental Changes in Thickness, Contractility, and Hypoxic Sensitivity of Newborn Lamb Cerebral Arteries

48-h Hypoxic exposure results in endothelium-dependent systemic vascular smooth muscle cell hyperpolarization

Contact Info

Product

Resources

About