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 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 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

Calcium sparks in mouse ventricular myocytes at physiological temperature

2003 ◽  
Vol 285 (4) ◽  
pp. H1495-H1505 ◽  
Author(s):  
Gregory R. Ferrier ◽  
Robin H. Smith ◽  
Susan E. Howlett
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Ryanodine Receptor ◽  
Rise Time ◽  
Room Temperature ◽  
Ventricular Myocytes ◽  
Field Stimulation ◽  
Receptor Function ◽  
Decay Times ◽  
Effects Of Temperature

In cardiac muscle, Ca2+ is released from the sarcoplasmic reticulum (SR) in units called Ca2+ sparks. Ca2+ spark characteristics have been studied almost entirely at room temperature. This study compares characteristics of spontaneous sparks detected with fluo 3 in resting mouse ventricular myocytes at 22 and 37°C. The incidence and frequency of Ca2+ sparks decreased dramatically at 37°C compared with 22°C. Also, spark amplitudes and times to peak were significantly reduced at 37°C. In contrast, spatial width and decay times were unchanged. During field stimulation, peak spatially averaged transients were similar at 22 and 37°C, and experiments with fura 2 demonstrated that diastolic and systolic Ca2+ concentrations were unchanged. However, SR Ca2+ content decreased significantly at 37°C. Restoration of SR Ca2+ by superfusion with 5 mM Ca2+ increased spark frequency but did not reverse the effects of temperature on spark parameters. Thus effects of temperature on spark frequency may reflect changes in SR stores, whereas changes in spark amplitude and rise time may reflect known effects of temperature on ryanodine receptor function.

scholarly journals Generation of dendritic Ca2+oscillations as a consequence of altered ryanodine receptor function in AD neurons

Channels ◽  
2011 ◽  
Vol 5 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Ivan Goussakov ◽  
Shreaya Chakroborty ◽  
Grace E. Stutzmann
Keyword(s):  
Ryanodine Receptor ◽  
Receptor Function

Sex Differences in Right Ventricular-Vascular Coupling and Pulmonary Artery Impedance in Response to Chronic Hypoxia and Recovery

2012 ◽  
Author(s):  
Aiping Liu ◽  
Lian Tian ◽  
Diana M. Tabima ◽  
Naomi C. Chesler
Keyword(s):  
Pulmonary Artery ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Pulmonary Artery Hypertension ◽  
Vascular Impedance ◽  
Female Predominance ◽  
Collagen Accumulation ◽  
Dominant Disease ◽  
Pulmonary Arterial

Pulmonary artery hypertension (PAH) is a female dominant disease (the female-to-male ratio is 4:1), characterized by small distal pulmonary arterial narrowing and large proximal arterial stiffening, which increase right ventricle (RV) afterload and ultimately lead to RV failure [1,2]. Our recent studies have shown that collagen accumulation induced by chronic hypoxia increases the stiffness of the large extralobar pulmonary arteries (PAs) [3], and affects pulmonary vascular impedance (PVZ) [4]. The role of collagen in the female predominance in developing PAH has not been explored to date.

Thromboxane inhibition reduces an early stage of chronic hypoxia-induced pulmonary hypertension in piglets

2005 ◽  
Vol 99 (2) ◽  
pp. 670-676 ◽  
Author(s):  
Candice D. Fike ◽  
Yongmei Zhang ◽  
Mark R. Kaplowitz
Keyword(s):  
Pulmonary Hypertension ◽  
Chronic Hypoxia ◽  
Early Stage ◽  
Pulmonary Arteries ◽  
Pulmonary Wedge Pressure ◽  
Thromboxane Synthase Inhibitor ◽  
Pulmonary Arterial ◽  
Synthase Inhibitor ◽  
Air Control ◽  
Arterial Responses

The pulmonary vasoconstrictor, thromboxane, may contribute to the development of pulmonary hypertension. Our objective was to determine whether a combined thromboxane synthase inhibitor-receptor antagonist, terbogrel, prevents pulmonary hypertension and the development of aberrant pulmonary arterial responses in newborn piglets exposed to 3 days of hypoxia. Piglets were maintained in room air (control) or 11% O2 (hypoxic) for 3 days. Some hypoxic piglets received terbogrel (10 mg/kg po bid). Pulmonary arterial pressure, pulmonary wedge pressure, and cardiac output were measured in anesthetized animals. A cannulated artery technique was used to measure responses to acetylcholine. Pulmonary vascular resistance for terbogrel-treated hypoxic piglets was almost one-half the value of untreated hypoxic piglets but remained greater than values for control piglets. Dilation to acetylcholine in preconstricted pulmonary arteries was greater for terbogrel-treated hypoxic than for untreated hypoxic piglets, but it was less for pulmonary arteries from both groups of hypoxic piglets than for control piglets. Terbogrel may ameliorate pulmonary artery dysfunction and attenuate the development of chronic hypoxia-induced pulmonary hypertension in newborns.

Thapsigargin stimulates increased NO activity in hypoxic hypertensive rat lungs and pulmonary arteries

1996 ◽  
Vol 80 (4) ◽  
pp. 1336-1344 ◽  
Author(s):  
M. Muramatsu ◽  
R. C. Tyler ◽  
D. M. Rodman ◽  
I. F. McMurtry
Keyword(s):  
Pulmonary Artery ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Male Rats ◽  
Pulmonary Vasculature ◽  
No Production ◽  
Low Concentrations ◽  
Pulmonary Vascular Endothelium ◽  
Increased Sensitivity ◽  
Stimulation Of

This study addressed the controversy of whether endothelium-derived nitric oxide (NO) activity is increased or decreased in the hypertensive pulmonary vasculature of chronically hypoxic rats. Thapsigargin, a receptor-independent Ca2+ agonist and stimulator of endothelial NO production, was used to compare NO-mediated vasodilation in perfused lungs and conduit pulmonary artery rings isolated from adult male rats either kept at Denver's altitude of 5,280 ft (control pulmonary normotensive rats) or exposed for 4-5 wk to the simulated altitude of 17,000 ft (chronically hypoxic pulmonary hypertensive rats). Under baseline conditions, thapsigargin (10(-9)-10(-7) M) caused vasodilation in hypertensive lungs and vasoconstriction in normotensive lungs. Whereas the sustained vasodilation in hypertensive lungs was reversed to vasoconstriction by the inhibitor of NO synthase N(omega)-nitro-L-arginine (L-NNA; 10(-4) M), a transient vasodilation to thapsigargin in acutely vasoconstricted normotensive lungs was potentiated. As measured by a chemiluminescence assay, the recirculated perfusate of hypertensive lungs accumulated considerably higher levels of NO-containing compounds that did normotensive lungs, and thapsigargin-induced stimulation of NO-containing compounds accumulation was greater in hypertensive than in normotensive lungs. Similarly, low concentrations of thapsigargin (10(-10)-10(-9) M) caused greater endothelium-dependent L-NNA-reversible relaxation of hypertensive than of normotensive pulmonary artery rings. The increased sensitivity of hypertensive arteries to thapsigargin-induced relaxation was eliminated in nominally Ca(2+)-free medium and was not mimicked by ryanodine, a releaser of intracellular Ca2+. These results with thapsigargin, which acts on endothelial cells to stimulate Ca2+ influx and a sustained rise in intracellular Ca2+ concentration, support the idea that pulmonary vascular endothelium-derived NO activity is increased rather than decreased in chronic hypoxia-induced pulmonary hypertension in rats.

Effects of hypoxia on density of beta-adrenergic receptors

1981 ◽  
Vol 50 (2) ◽  
pp. 363-366 ◽  
Author(s):  
N. F. Voelkel ◽  
L. Hegstrand ◽  
J. T. Reeves ◽  
I. F. McMurty ◽  
P. B. Molinoff
Keyword(s):  
High Altitude ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Low Dose ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Altitude Exposure

Exposure to chronic hypoxia results in a lower resting heart rate and a blunted cardiovascular responsiveness to beta-adrenergic receptor stimulation. Possible effects of acclimatization to high altitude on the binding of [125I]iodohydroxybenzylpindolol to beta-adrenergic receptors on membranes of right and left ventricles of rat heart were determined. Chronic high-altitude exposure led to a decrease in the density of beta-adrenergic receptors in nonhypertrophied left ventricles as well as in hypertrophied right ventricles. The affinity of the receptor for the radioligand was not changed by the exposure to high altitude, suggesting that the properties of the receptor were not affected. Basal and isoproterenol-stimulated adenylate cyclase activities were decreased in membranes prepared from hearts and pulmonary arteries of rats acclimatized to high altitude. The loss of cardiac beta-adrenergic receptors in rats adapted to high altitude was prevented by the chronic coadministration of a low dose of DL-propranolol. The results suggest that changes in beta-adrenergic receptor density may partially explain the hemodynamic adaptation that occurs with chronic hypoxia. These decreases may be due to a loss of functional beta-adrenergic receptors caused by chronically elevated concentrations of circulating neurally released catecholamines.

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