scholarly journals Hypercapnia Attenuates the Hypoxia-Induced Blunting of the Reactivity in Chronically Hypoxic Rats

2013 ◽  
pp. 585-588
Author(s):  
M. ŽALOUDÍKOVÁ ◽  
J. HERGET ◽  
M. VÍZEK
Keyword(s):  
Lung Injury ◽  
Biochemical Markers ◽  
Vascular Reactivity ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Transmural Pressure ◽  
Small Vessel ◽  
Vessel Size ◽  
Pulmonary Vessels ◽  
Maximal Tension

Chronic hypoxia causes oxidative injury of pulmonary vessels and attenuates their reactivity to different stimuli. When combined with hypercapnia, biochemical markers of this injury are reduced but the effect of concomitant hypoxia and hypercapnia on vascular reactivity is not fully understood. This study was therefore designed to test whether hypercapnia can prevent also the hypoxia-induced loss of reactivity of pulmonary vessels. The reactivity of vessels from rats exposed either to hypoxia or hypoxia combined with hypercapnia was tested using a small vessel myograph (M 500A, Linton, Norfolk, GB). The second and third intrapulmonary branches of pulmonary arteries were isolated under a dissecting microscope from lungs of 8 control rats (group N), 6 rats exposed to hypoxia for 5 days (isobaric, 10 % O2, group H) and 7 rats exposed to hypoxia combined with hypercapnia for 5 days (10 % O2, 5 % CO2, group H+CO2). The transmural pressure was set by automatic normalization to 30 mm Hg. The vessel size did not vary among the groups. After stabilization we challenged the vessels twice with KCl (80 mM) and once with PGF2α (0.1 mM). There were no significant differences in KCl induced contractions among the groups. The responses to PGF2α were expressed as a ratio to the maximal tension obtained by the exposure to 80 mM KCl. Contractions induced by PGF2α were markedly reduced in group H (0.07±0.02) and in group H+CO2 (0.26±0.03) in comparison with group N (0.83±0.07). The vessels of group H responded to PGF2α less than those of group H+CO2. However we observed the attenuated reactivity also in group H+CO2 in comparison with N. Hypercapnia therefore partially blunted the hypoxia-induced loss of reactivity in pulmonary arteries. This finding supports the hypothesis that hypercapnia significantly alters the nature of lung injury induced by chronic hypoxia.

Vasodilatory Action of the Calcium Antagonist Amlodipine on Large and Resistance Pulmonary Arteries from Normoxic and Chronically Hypoxic Rats

1993 ◽  
Vol 85 (3) ◽  
pp. 361-366 ◽  
Author(s):  
Paul A. Woodmansey ◽  
Fan Zhang ◽  
Kevin S. Channer ◽  
Alyn H. Morice
Keyword(s):  
Calcium Antagonist ◽  
Chronic Hypoxia ◽  
Potent Inhibitor ◽  
Pulmonary Arteries ◽  
Rat Aorta ◽  
Lumen Diameter ◽  
Pulmonary Resistance ◽  
Pulmonary Vessels ◽  
Resistance Vessels ◽  
Vasodilatory Action

1. Isolated rat aorta and pulmonary arteries were maximally precontracted with 100 mmol/l KCl, and the vasorelaxation due to the dihydropyridine calcium antagonist amlodipine was measured. The response of large pulmonary arteries (mean lumen diameter 983 μm) was directly compared with that of isolated pulmonary resistance vessels (mean lumen diameter 259 μm) from both normoxic animals and animals exposed to chronic hypoxia. 2. Amlodipine caused a significant relaxation of aorta (P <0.001). A significant relaxation of large and resistance pulmonary arteries from both normoxic and chronically hypoxic animals was also demonstrated at all doses tested (P <0.05) or less). 3. Amlodipine produced significantly more relaxation in pulmonary resistance vessels than in large pulmonary arteries from both normoxic and chronically hypoxic rats (P <0.02). 4. The action of amlodipine was slow in onset and persistent in all vessels studied. In the pulmonary vessels from normoxic animals both the rate of onset and the magnitude of effect was proportional to the drug concentration (P <0.001). 5. These results demonstrate that amlodipine is a potent inhibitor of KCl-induced contractions in rat pulmonary arteries with a preferential action in pulmonary resistance vessels.

Store-operated channels in the pulmonary circulation of high- and low-altitude neonatal lambs

2013 ◽  
Vol 304 (8) ◽  
pp. L540-L548 ◽  
Author(s):  
Daniela Parrau ◽  
Germán Ebensperger ◽  
Emilio A. Herrera ◽  
Fernando Moraga ◽  
Raquel A. Riquelme ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Resistance ◽  
Vascular Reactivity ◽  
Chronic Hypoxia ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Pulmonary Arteries ◽  
Arterial Blood ◽  
Low Altitude

We determined whether store-operated channels (SOC) are involved in neonatal pulmonary artery function under conditions of acute and chronic hypoxia, using newborn sheep gestated and born either at high altitude (HA, 3,600 m) or low altitude (LA, 520 m). Cardiopulmonary variables were recorded in vivo, with and without SOC blockade by 2-aminoethyldiphenylborinate (2-APB), during basal or acute hypoxic conditions. 2-APB did not have effects on basal mean pulmonary arterial pressure (mPAP), cardiac output, systemic arterial blood pressure, or systemic vascular resistance in both groups of neonates. During acute hypoxia 2-APB reduced mPAP and pulmonary vascular resistance in LA and HA, but this reduction was greater in HA. In addition, isolated pulmonary arteries mounted in a wire myograph were assessed for vascular reactivity. HA arteries showed a greater relaxation and sensitivity to SOC blockers than LA arteries. The pulmonary expression of two SOC-forming subunits, TRPC4 and STIM1, was upregulated in HA. Taken together, our results show that SOC contribute to hypoxic pulmonary vasoconstriction in newborn sheep and that SOC are upregulated by chronic hypoxia. Therefore, SOC may contribute to the development of neonatal pulmonary hypertension. We propose SOC channels could be potential targets to treat neonatal pulmonary hypertension.

scholarly journals Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calves

2011 ◽  
Vol 301 (5) ◽  
pp. H1810-H1818 ◽  
Author(s):  
Lian Tian ◽  
Steven R. Lammers ◽  
Philip H. Kao ◽  
Mark Reusser ◽  
Kurt R. Stenmark ◽  
...  
Keyword(s):  
Mechanical Behavior ◽  
Wall Thickness ◽  
Arterial Wall ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Opening Angle ◽  
Histological Structure ◽  
Arterial Remodeling ◽  
Stiffness Ratio ◽  
Arterial Wall Thickness

Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, residual stretch, and histology of proximal PAs in both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH), compared their changes due to chronic hypoxia across species, and proposed a two-layer mechanical model of artery to relate the opening angle to the stiffness ratio of the PA outer to inner layer. We found that the proximal PA remodeling in calves was quite different from that in rats. In rats, the arterial wall thickness, inner diameter, and outer layer thickness fraction all increased dramatically in PH and the opening angle decreased significantly, whereas in calves, only the arterial wall thickness increased in PH. The proposed model predicted that the stiffness ratio of the calf proximal PAs changed very little from control to hypertensive group, while the decrease of opening angle in rat proximal PAs in response to chronic hypoxia was approximately linear to the increase of the stiffness ratio. We conclude that the arterial remodeling in rat and calf proximal PAs is different and the change of opening angle can be linked to the change of the arterial histological structure and mechanics.

Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia

2007 ◽  
Vol 292 (3) ◽  
pp. L678-L684 ◽  
Author(s):  
Yuansheng Gao ◽  
Ada D. Portugal ◽  
Sewite Negash ◽  
Weilin Zhou ◽  
Lawrence D. Longo ◽  
...  
Keyword(s):  
High Altitude ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Regulatory Subunit ◽  
Fourth Generation ◽  
Minor Effect ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Rock Activity

An increase in Rho kinase (ROCK) activity is implicated in chronic hypoxia-induced pulmonary hypertension. In the present study, we determined the role of ROCKs in cGMP-dependent protein kinase (PKG)-mediated pulmonary vasodilation of fetal lambs exposed to chronic hypoxia. Fourth generation pulmonary arteries were isolated from near-term fetuses (∼140 days of gestation) delivered from ewes exposed to chronic high altitude hypoxia for ∼110 days and from control ewes. In vessels constricted to endothelin-1, 8-bromoguanosine-cGMP (8-Br-cGMP) caused a smaller relaxation in chronically hypoxic (CH) vessels compared with controls. Rp-8-Br-PET-cGMPS, a PKG inhibitor, attenuated relaxation to 8-Br-cGMP in control vessels to a greater extent than in CH vessels. Y-27632, a ROCK inhibitor, significantly potentiated 8-Br-cGMP-induced relaxation of CH vessels and had only a minor effect in control vessels. The expression of PKG was increased but was not accompanied with an increase in the activity of the enzyme in CH vessels. The expression of type II ROCK and activity of ROCKs were increased in CH vessels. The phosphorylation of threonine (Thr)696 and Thr850 of the regulatory subunit MYPT1 of myosin light chain phosphatase was inhibited by 8-Br-cGMP to a lesser extent in CH vessels than in controls. The difference was eliminated by Y-27632. These results suggest that chronic hypoxia in utero attenuates PKG-mediated relaxation in pulmonary arteries, partly due to inhibition of PKG activity and partly due to enhanced ROCK activity. Increased ROCK activity may inhibit PKG action through increased phosphorylation of MYPT1 at Thr696 and Thr850.

scholarly journals Combined influence of ontogeny and chronic hypoxia on ryanodine receptor function in sheep pulmonary arteries and myocytes

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Scott Hadley ◽  
Quintin Blood ◽  
Peterson Le ◽  
Demosthenes G Papamatheakis ◽  
Lawrence D Longo ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Receptor Function

scholarly journals Nonselective cation channel function in sheep pulmonary arteries is affected by postnatal maturation and chronic hypoxia

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Demosthenes G Papamatheakis ◽  
Srilakshmi Vemulakonda ◽  
Quintin Blood ◽  
Travis T Merritt ◽  
Sidney Lauw ◽  
...  
Keyword(s):  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Cation Channel ◽  
Nonselective Cation Channel ◽  
Postnatal Maturation ◽  
Channel Function

Repeated lung injury due to alpha-naphthylthiourea causes right ventricular hypertrophy in rats

1984 ◽  
Vol 56 (2) ◽  
pp. 388-396 ◽  
Author(s):  
N. S. Hill ◽  
R. F. O'Brien ◽  
S. Rounds
Keyword(s):  
Pulmonary Hypertension ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Vascular Reactivity ◽  
Tween 80 ◽  
Left Ventricular ◽  
Right Ventricular Hypertrophy ◽  
Arterial Blood

Acute lung injury due to alpha-naphthylthiourea (ANTU) is associated with increased permeability edema, transient pulmonary hypertension, and increased vascular reactivity. We sought to determine whether repeated administration of ANTU caused right ventricular hypertrophy. Rats were injected weekly for 4 wk with ANTU or an equivalent volume of the vehicle Tween 80. Rats injected repeatedly with ANTU in doses of 5–10 mg/kg body wt had increased ratios of right ventricular to left ventricular plus septal weights. The right ventricular hypertrophy in ANTU-treated rats was associated with right ventricular systolic hypertension. Repeated injections of ANTU also caused transient pulmonary edema after each dose, as evidenced by increased wet-to-dry lung weight ratios after 4 h, which returned to normal by 24 h. Lungs isolated from ANTU-injected rats had greater pressor responses to hypoxia and to angiotensin II than lungs from Tween 80-injected rats. Pressure-flow curves of isolated lungs, arterial blood gases, and hematocrits were similar in rats treated repetitively with ANTU or Tween alone. Lung histology was also similar in ANTU and control lungs, as were measurements of arterial medial thickness and ratios of numbers of arteries/100 alveoli, indicating that substantial vascular remodeling had not occurred. Thus, four weekly ANTU injections in rats caused right ventricular hypertrophy, probably due to pulmonary hypertension. We speculate that the pulmonary hypertension was due, at least in part, to sustained vasoconstriction, which somehow resulted from repeated acute lung injury.

Flow-induced responses in cat isolated pulmonary arteries

1997 ◽  
Vol 83 (5) ◽  
pp. 1617-1622 ◽  
Author(s):  
Larissa A. Shimoda ◽  
Nan A. Norins ◽  
Jane A. Madden
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pulmonary Arteries ◽  
Transmural Pressure ◽  
Induced Responses ◽  
Synthesis Inhibitor ◽  
Cell Deformability ◽  
Endothelin 1 ◽  
Kinase C ◽  
Intracellular Ca

Shimoda, Larissa A., Nan A. Norins, and Jane A. Madden. Flow-induced responses in cat isolated pulmonary arteries. J. Appl. Physiol.83(5): 1617–1622, 1997.—Isolated, cannulated, endothelium-intact cat pulmonary arteries, averaging 692 ± 104 μm in diameter, were set at a transmural pressure of 10 mmHg and monitored with a video system. Intraluminal flow was increased in steps from 0 to 1.6 ml/min by using a syringe pump. An electronic system held pressure constant by changing outflow resistance. Flow-diameter curves were generated in physiological saline solution. At constant transmural pressure, the arteries constricted in response to increased intraluminal flow. Constriction was not affected by removing extracellular Ca2+ but was abolished after treatment with ryanodine to deplete intracellular Ca2+ stores, with the endothelin-1 synthesis inhibitor phosphoramidon, with the endothelin A-receptor antagonist BQ-123, with the protein kinase C inhibitor staurosporine, or with glutaraldehyde to reduce endothelial cell deformability. The results indicate that isolated pulmonary arteries can constrict in response to intraluminal flow and suggest that constriction is mediated by endothelin-1 and depends on intracellular Ca2+ release and protein kinase C activation.

Ginkgo Biloba Extract (Egb 761) Modulates Bleomycin-induced Acute Lung Injury in Rats

2001 ◽  
Vol 87 (6) ◽  
pp. 417-422 ◽  
Author(s):  
Aiman S El-Khatib ◽  
Adel M Moustafa ◽  
Abdel-Aziz H Abdel-Aziz ◽  
Othman A Al-Shabanah ◽  
Hassan A El-Kashef
Keyword(s):  
Alkaline Phosphatase ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Artery ◽  
Lung Tissue ◽  
Ginkgo Biloba ◽  
Biochemical Markers ◽  
Ginkgo Biloba Extract ◽  
Slight Reduction ◽  
Egb 761

The effect of Ginkgo biloba extract (EGb 761) on bleomycin (BLM)-induced acute lung injury was studied in rats. The responsiveness of isolated pulmonary arterial rings to 5-hydroxytryptamine (5-HT) as well as the levels of some relevant biochemical markers in the lung tissue were taken as evidence for the acute lung injury. BLM was given intraperitoneally at a dose of 15 mg/kg/day for five consecutive days. It was found that BLM treatment attenuated the vasoconstrictor effect of 5-HT on the isolated pulmonary arteries. In lung tissues BLM also elevated the level of lipid peroxides and enhanced the activity of glutathione peroxidase. On the other hand, the level of glutathione and the activity of alkaline phosphatase were reduced. Body weight, lung weight and tissue glutathione-S-transferase activity were, however, not altered. Oral administration of EGb 761 at a dose of 100 mg/kg/day for five consecutive days did not alter any of the chosen biochemical parameters in the lung tissue except for a slight reduction in alkaline phosphatase activity. However, treatment with EGb 761 reduced the responsiveness of the pulmonary artery to 5-HT. Administration of EGb 761 (100 mg/kg/day; po) two hours prior to BLM (15 mg/kg/day; ip), for five consecutive days blunted the occurrence of further reduction in the vasoconstrictor response of the pulmonary artery to 5-HT. Furthermore, EGb 761 tended to normalize BLM-induced alterations in the measured biochemical markers in the lung tissue. The apparent modulatory influence of EGb 761 on BLM-induced acute lung injury stems, at least in part, from its beneficial free radical scavenging properties that provide the extract with antioxidant activity.

Sign in / Sign up

Export Citation Format

Share Document