scholarly journals The Xanthine Derivative KMUP-1 Attenuates Serotonin-Induced Vasoconstriction and K+-Channel Inhibitory Activity via the PKC Pathway in Pulmonary Arteries

2015 ◽  
Vol 11 (6) ◽  
pp. 633-642 ◽  
Author(s):  
Zen-Kong Dai ◽  
Yu-Wei Liu ◽  
Jong-Hau Hsu ◽  
Jwu-Lai Yeh ◽  
Ing-Jun Chen ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Pulmonary Arteries ◽  
K Channel ◽  
Xanthine Derivative

Adenine nucleotides via activation of ATP-sensitive K+ channels modulate hypoxic response in rat pulmonary artery

1996 ◽  
Vol 270 (5) ◽  
pp. L803-L809 ◽  
Author(s):  
K. Shigemori ◽  
T. Ishizaki ◽  
S. Matsukawa ◽  
A. Sakai ◽  
T. Nakai ◽  
...  
Keyword(s):  
Adenine Nucleotides ◽  
Pulmonary Arteries ◽  
K Channel ◽  
Dependent Manner ◽  
Atp Content ◽  
K Channels ◽  
Freeze Dried ◽  
Pulmonary Arterial ◽  
Induced Changes ◽  
Isolated Rat

We examined the role of ATP-sensitive K+ channels in hypoxic pulmonary vasoconstriction, using isolated rat pulmonary arterial rings. Isolated rat pulmonary arterial rings displayed a rapid contraction followed by relaxation under hypoxic conditions. The ATP-sensitive K+ channel blocker glibenclamide (concentration > 1 microM) or a hyperglycemic buffer (15 mM glucose) attenuated the hypoxic relaxation in a dose-dependent manner but did not affect the hypoxia-induced contraction. To examine the relationship between hypoxia, energy, and redox state, intracellular levels of adenine nucleotides and pyridine coenzymes were determined by high-performance liquid chromatography in freeze-dried isolated rat pulmonary arteries at three time points (0, 4, and 10 min) before and during hypoxia. Hypoxia time dependently decreased the ATP content and the ATP-to-ADP ratio and increased the ADP and the AMP content in association with a rapid increase in the NADH and the NADH-to-NAD+ ratio. Hyperglycemic buffer (15 mM glucose) suppressed the hypoxia-induced changes of the adenine nucleotides (the decrease of the ATP content and the ATP-to-ADP ratio) but did not affect the hypoxia-induced changes of the NADH and the NADH-to-NAD+ ratio. Hypoxia did not affect the NADP+ or the NADPH content of pulmonary arteries. These findings indicate that an ATP-sensitive K+ channel regulates the tone of rat pulmonary arteries. Furthermore, an imbalance of the energy state may be involved in ATP-sensitive K+ channel activation during hypoxic vasorelaxation.

scholarly journals Hydrogen Sulfide Metabolism and Pulmonary Hypertension

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1477
Author(s):  
Lukas Roubenne ◽  
Roger Marthan ◽  
Bruno Le Le Grand ◽  
Christelle Guibert
Keyword(s):  
Pulmonary Hypertension ◽  
Hydrogen Sulfide ◽  
Pulmonary Circulation ◽  
Pulmonary Arteries ◽  
K Channel ◽  
Protective Effects ◽  
Pulmonary Arterial ◽  
Regulatory Functions

Pulmonary hypertension (PH) is a severe and multifactorial disease characterized by a progressive elevation of pulmonary arterial resistance and pressure due to remodeling, inflammation, oxidative stress, and vasoreactive alterations of pulmonary arteries (PAs). Currently, the etiology of these pathological features is not clearly understood and, therefore, no curative treatment is available. Since the 1990s, hydrogen sulfide (H2S) has been described as the third gasotransmitter with plethoric regulatory functions in cardiovascular tissues, especially in pulmonary circulation. Alteration in H2S biogenesis has been associated with the hallmarks of PH. H2S is also involved in pulmonary vascular cell homeostasis via the regulation of hypoxia response and mitochondrial bioenergetics, which are critical phenomena affected during the development of PH. In addition, H2S modulates ATP-sensitive K+ channel (KATP) activity, and is associated with PA relaxation. In vitro or in vivo H2S supplementation exerts antioxidative and anti-inflammatory properties, and reduces PA remodeling. Altogether, current findings suggest that H2S promotes protective effects against PH, and could be a relevant target for a new therapeutic strategy, using attractive H2S-releasing molecules. Thus, the present review discusses the involvement and dysregulation of H2S metabolism in pulmonary circulation pathophysiology.

Mechanisms of hypoxic vasodilation in ferret pulmonary arteries

1995 ◽  
Vol 269 (3) ◽  
pp. L351-L357 ◽  
Author(s):  
C. M. Wiener ◽  
M. R. Banta ◽  
M. S. Dowless ◽  
N. A. Flavahan ◽  
J. T. Sylvester
Keyword(s):  
Pulmonary Arteries ◽  
Katp Channels ◽  
Isometric Tension ◽  
K Channel ◽  
Pulmonary Vasodilation ◽  
Fifth Generation ◽  
Endothelial Denudation ◽  
Vasoconstrictor Response ◽  
Hypoxic Vasodilation ◽  
Oxide Synthase

To investigate the mechanism of hypoxic pulmonary vasodilation we measured isometric tension in rings from ferret third- to fifth-generation intrapulmonary arteries mounted in organ baths (37 degrees C, 28% O2-5% CO2). After precontraction with phenylephrine (PE), hypoxia caused a brief transient vasoconstriction followed by marked vasodilation. Endothelial denudation did not affect the steady-state response. In vessels without endothelium, inhibition of cyclooxygenase and nitric oxide synthase had no effect on the response to hypoxia. Inhibition of ATP-dependent K+ channels (KATP) with glibenclamide, linogliride, or tolbutamide had no effect on normoxic tone before PE or the vasoconstrictor response to PE but inhibited hypoxic vasodilation. Inhibition of Ca(2+)-activated K+ (KCa) channels with charybdotoxin potentiated the vasoconstrictor response to PE but had no effect on hypoxic vasodilation. The nonspecific K(+)-channel inhibitor tetraethyl-ammonium (TEA) potentiated the response to PE and inhibited hypoxic vasodilation. Glibenclamide plus TEA inhibited hypoxic vasodilation more than either agent alone, suggesting that TEA inhibited the KATP-channel independent vasodilation. These results suggest that in isolated ferret pulmonary arteries hypoxia causes vasodilation partially by activating smooth muscle KATP channels. Activation of a TEA-sensitive channel that is not a KATP or KCa channel may also contribute to hypoxic vasodilation.

Voltage-gated K+-channel activity in ovine pulmonary vasculature is developmentally regulated

2000 ◽  
Vol 278 (6) ◽  
pp. L1297-L1304 ◽  
Author(s):  
David N. Cornfield ◽  
Connie B. Saqueton ◽  
Valerie A. Porter ◽  
Jean Herron ◽  
Ernesto Resnik ◽  
...  
Keyword(s):  
Acute Hypoxia ◽  
Pulmonary Arteries ◽  
Developmental Changes ◽  
Pulmonary Vasculature ◽  
K Channel ◽  
Mrna Levels ◽  
Channel Activity ◽  
Developmentally Regulated ◽  
Voltage Gated ◽  
Channel Expression

To examine mechanisms underlying developmental changes in pulmonary vascular tone, we tested the hypotheses that 1) maturation-related changes in the ability of the pulmonary vasculature to respond to hypoxia are intrinsic to the pulmonary artery (PA) smooth muscle cells (SMCs); 2) voltage-gated K+(Kv)-channel activity increases with maturation; and 3) O2-sensitive Kv2.1 channel expression and message increase with maturation. To confirm that maturational differences are intrinsic to PASMCs, we used fluorescence microscopy to study the effect of acute hypoxia on cytosolic Ca2+concentration ([Ca2+]i) in SMCs isolated from adult and fetal PAs. Although PASMCs from both fetal and adult circulations were able to sense an acute decrease in O2 tension, acute hypoxia induced a more rapid and greater change in [Ca2+]i in magnitude in PASMCs from adult compared with fetal PAs. To determine developmental changes in Kv-channel activity, the effects of the K+-channel antagonist 4-aminopyridine (4-AP) were studied on fetal and adult PASMC [Ca2+]i. 4-AP (1 mM) caused PASMC [Ca2+]i to increase by 94 ± 22% in the fetus and 303 ± 46% in the adult. Kv-channel expression and mRNA levels in distal pulmonary arteries from fetal, neonatal, and adult sheep were determined through the use of immunoblotting and semiquantitative RT-PCR. Both Kv2.1-channel protein and mRNA expression in distal pulmonary vasculature increased with maturation. We conclude that there are maturation-dependent changes in PASMC O2 sensing that may render the adult PASMCs more responsive to acute hypoxia.

Effects of inhibitors of EDRF and EDHF on vasoreactivity of perfused rat lungs

1991 ◽  
Vol 260 (2) ◽  
pp. L97-L104 ◽  
Author(s):  
K. Hasunuma ◽  
T. Yamaguchi ◽  
D. M. Rodman ◽  
R. F. O'Brien ◽  
I. F. McMurtry
Keyword(s):  
Vascular Reactivity ◽  
Pressor Response ◽  
Pulmonary Arteries ◽  
K Channel ◽  
Channel Blockers ◽  
Hypoxic Response ◽  
K Channels ◽  
Pulmonary Vasodilation ◽  
Rat Lungs ◽  
Hypoxic Vasoconstriction

Recent studies indicate that the endothelium of isolated rat pulmonary arteries releases two different factors, endothelium-derived relaxing factor (EDRF) and hyperpolarizing factor (EDHF), which participate in histamine- and acetylcholine-induced relaxation. There is evidence for EDRF vasoreactivity in perfused lungs, but a role for EDHF, which hyperpolarizes vascular smooth muscle by activating membrane K+ channels, has not been reported. We used the inhibitors of EDRF, 20 microM hemoglobin, 200 microM NG-mono-methyl-L-arginine, and 2 mM L-canavanine, the nonselective blocker of K+ channels, 10 mM tetraethylammonium (TEA), and the inhibitor of ATP-sensitive K+ channels, 20 microM glibenclamide, to compare the roles of EDRF and EDHF in the vasoregulation of meclofenamate-treated, salt solution-perfused rat lungs. The three EDRF inhibitors had little or no effect on baseline perfusion pressure, but each potentiated the peak pressor response to airway hypoxia. Neither of them inhibited the pulmonary vasodilation to 5 microM histamine. TEA, but not glibenclamide, increased baseline pressure and potentiated the peak hypoxic response. Both K+ channel blockers, but not the EDRF inhibitors, also prolonged the hypoxic response by reducing the rate of spontaneous vasodilation. TEA, but not glibenclamide, inhibited histamine vasodilation. These results suggest roles for both EDRF and EDHF in the control of rat pulmonary vascular reactivity. EDRF is apparently not responsible for the low vascular tone of the normoxic lung and does not mediate the vasodilation to histamine, but it does modulate the hypoxic pressor response. The exact role of EDHF is uncertain, but it may also modulate hypoxic vasoconstriction and mediate at least part of the histamine vasodilation.

Sign in / Sign up

Export Citation Format

Share Document