Endothelin-1-induced pulmonary arterial dilation is reduced by N omega-nitro-L-arginine in fetal lambs

1992 ◽  
Vol 72 (5) ◽  
pp. 1730-1734 ◽  
Author(s):  
M. L. Tod ◽  
S. Cassin
Keyword(s):  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Vascular Occlusion ◽  
Pressure Gradients ◽  
Endothelin 1 ◽  
Pulmonary Vasodilator ◽  
Pulmonary Capillary ◽  
Occlusion Technique ◽  
Pulmonary Arterial ◽  
Arterial Dilation

Endothelin-1 (ET-1) is a pulmonary vasodilator in the unventilated fetal lamb. The site and mechanism of this vasodilator response were investigated in isolated blood-perfused lungs from nine fetal lambs delivered at 127–140 days gestation. The vascular occlusion technique was used to partition the total pulmonary pressure gradient into pressure gradients across large and small arteries (delta PLA and delta PSA, respectively) and veins (delta PV). Injection of ET-1 (74 ng/kg) into the pulmonary artery significantly decreased delta PLA from 12.4 +/- 2.1 to 5.2 +/- 1.1 mmHg and delta PSA from 49.2 +/- 2.7 to 31.3 +/- 4.9 mmHg. The pressure measured by double occlusion, an estimate of pulmonary capillary pressure, was not altered by ET-1 (15.5 +/- 1.0 vs. 14.8 +/- 1.0 mmHg), indicating that ET-1 had no effect on pulmonary veins. Addition of N omega-nitro-L-arginine (estimated perfusate concentration 2–6 mM), an analogue of L-arginine that inhibits the production of endothelium-derived relaxing factor (EDRF), significantly attenuated the dilator responses to acetylcholine (10 micrograms) and ET-1 (74 ng/kg) by 35 and 56%, respectively. These results in unventilated fetal lungs indicate that 1) ET-1 dilates both large and small pulmonary arteries with no effect on pulmonary veins, and 2) this effect is mediated in part through the action of the EDRF pathway.

Sites of inhaled NO-induced vasodilation during hypoxia and U-46619 infusion in isolated lamb lungs

1995 ◽  
Vol 268 (4) ◽  
pp. H1422-H1427 ◽  
Author(s):  
M. L. Tod ◽  
D. C. O'Donnel ◽  
J. B. Gordon
Keyword(s):  
Pressure Gradient ◽  
Pulmonary Veins ◽  
Vascular Occlusion ◽  
Similar Degree ◽  
Pressure Gradients ◽  
Small Arteries ◽  
Pulmonary Vasoconstriction ◽  
Occlusion Technique ◽  
Inhaled No ◽  
Rapid Binding

The sites of relaxation in response to inhaled nitric oxide (NO) were investigated using the vascular occlusion technique in isolated blood-perfused lungs from 1- to 3-mo-old lambs. In one group of 10 lungs, inhaled NO (45 ppm) was administered during hypoxia- and U-46619-induced pulmonary vasoconstriction. In a second group of 5 lungs, responses to inhaled NO and infused sodium nitroprusside (SNP, 3 micrograms.kg-1.min-1) during U-46619-induced hypertension were compared. Hypoxia caused significant pulmonary vasoconstriction, with increases in the pressure gradients of large and small arteries and small veins, as defined by vascular occlusion. Inhaled NO significantly reduced the total pulmonary pressure gradient by 67% and relaxed both large and small arteries. Infusion of U-46619 caused significant increases in all segmental pressure gradients. While inhaled NO was effective in relaxing the large and small arteries and the small veins, it had no effect on the large veins. Infusions of SNP, a nitrosovasodilator thought to act like endogenous NO, caused a similar degree of total relaxation as NO (81 vs. 77%, respectively). However, in contrast to inhaled NO, SNP was effective in reducing the pressure gradient of the large pulmonary veins. These results suggest that rapid binding to and thus inactivation of inhaled NO by hemoglobin limit its efficacy as a pulmonary venous dilator.

Venous occlusion measurement of pulmonary capillary pressure: effects of embolization

1987 ◽  
Vol 63 (6) ◽  
pp. 2340-2342 ◽  
Author(s):  
R. J. Roselli ◽  
R. E. Parker
Keyword(s):  
Capillary Pressure ◽  
Pulmonary Arteries ◽  
Arterial Embolization ◽  
Venous Occlusion ◽  
Pressure Effects ◽  
Pulmonary Capillary ◽  
Pulmonary Capillary Pressure ◽  
Occlusion Technique ◽  
Pulmonary Arterial ◽  
Significant Underestimation

The effects of pulmonary arterial embolization on calculated pulmonary capillary pressure as determined by the venous occlusion technique are examined using a simple pressure-flow model for the lung. It is predicted that pulmonary, arterial embolization can induce significant underestimation of pulmonary capillary pressure in flowing vessels. This underestimation is related to the percent of vessels embolized and the caliber of pulmonary arteries that are embolized (i.e., the size of the emboli). Experimental verification of these theoretical findings is necessary before the conclusions can be extended to the interpretation of venous occlusion experiments in the lung.

Chronic hypoxia selectively augments endothelium-dependent pulmonary arterial vasodilation

1996 ◽  
Vol 270 (3) ◽  
pp. H888-H896 ◽  
Author(s):  
T. C. Resta ◽  
B. R. Walker
Keyword(s):  
Chronic Hypoxia ◽  
K Channel ◽  
Channel Blockers ◽  
No Donors ◽  
Question Mark ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial ◽  
Arterial Dilation ◽  
Spermine Nonoate ◽  
Increased Activity

We have previously demonstrated that chronic hypoxia (CH) augments pulmonary arterial dilation to the endothelium-derived nitric oxide (EDNO)-dependent pulmonary vasodilator arginine vasopressin (AVP). The present study examined 1) whether this enhanced vasoreactivity is observed with other agents that act by stimulating constitutive NO synthase (cNOS), 2) whether CH increases arterial vascular smooth muscle sensitivity to NO, and 3) whether endogenous endothelin (ET) or an endothelium-derived hyperpolarizing factor (EDHF) contributes to this altered arterial reactivity following CH. We examined responses to the receptor-mediated EDNO-dependent dilators histamine and ET-1, the nonreceptor-mediated EDNO-dependent dilator ionomycin, and the NO donors 1, 3-propanediamine, N- inverted question mark4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino] butyl inverted question mark (spermine NONOate) and S-nitroso-N-acetylpenicillamine (SNAP) in U-46619-constricted, isolated perfused lungs from control and CH rats. Additional experiments examined responses to AVP in the presence of the ET-receptor antagonist PD-145065 or the K+ channel blockers glibenclamide or tetraethylammonium (TEA) in lungs from each group. Microvascular pressure was assessed by double occlusion, allowing calculation of segmental resistances. Total and arterial vasodilatory responses to histamine, ET-1, and ionomycin were augmented in lungs from CH vs. control animals. However, CH did not alter the vasodilation to spermine NONOate or SNAP. PD-145065, glibenclamide, and TEA had no effect on responses to AVP in either group. We conclude that increased activity of arterial cNOS may be responsible for the augmented pulmonary arterial dilation to EDNO-dependent vasodilators following CH.

scholarly journals Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Sebastian Steven ◽  
Matthias Oelze ◽  
Moritz Brandt ◽  
Elisabeth Ullmann ◽  
Swenja Kröller-Schön ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Whole Blood ◽  
Pulmonary Arteries ◽  
Vascular Wall ◽  
Pentaerythritol Tetranitrate ◽  
Endothelin 1 ◽  
Pulmonary Arterial

Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined.Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells.Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

Chronic lung lymph fistula that only drains the left lung

1995 ◽  
Vol 269 (4) ◽  
pp. R943-R947
Author(s):  
Y. Kikuchi ◽  
H. Nakazawa ◽  
D. L. Traber
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Mediastinal Lymph Node ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Left Lung ◽  
Lymph Flow ◽  
Pulmonary Arterial ◽  
The Right ◽  
Arteries And Veins

We developed a chronic lung fistula that drains only the left lung, allowing for evaluation of injury in a single lung. To remove lymph drainage from the right lung into the caudal mediastinal lymph node, the right lower pulmonary ligament was severed. Pneumatic occluders were placed on the left pulmonary arteries and veins. To ensure that lymph drained from only the left lung, we increased the right pulmonary arterial pressure (RPAP) from 21.2 +/- 0.5 to 36.5 +/- 0.6 mmHg. The left pulmonary arterial pressure (LPAP) was kept at wedge pressure level for 1 h by inflating pneumatic occluders. Lymph flow from the left lung fistula was stable during this occlusion. Six hours after recovery was increased the LPAP from a baseline level of 19.1 +/- 1.0 to 36.4 +/- 0.9 mmHg and the RPAP from 21.2 +/- 0.5 to 38.0 +/- 0.8 mmHg for 2 h by inflating the pneumatic occluders on the left and right pulmonary veins. Lymph flow increased from 5.3 +/- 1.0 to 28.0 +/- 2.9 ml/h. Reflection coefficient was calculated at 0.80 +/- 0.02.

Pulmonary vascular response to leukotriene D4 in unanesthetized sheep: role of thromboxane

1986 ◽  
Vol 60 (3) ◽  
pp. 765-769 ◽  
Author(s):  
T. C. Noonan ◽  
A. B. Malik
Keyword(s):  
Capillary Pressure ◽  
Pulmonary Veins ◽  
Thromboxane B2 ◽  
Base Line ◽  
Vascular Response ◽  
Leukotriene D4 ◽  
Pulmonary Hemodynamic ◽  
Pulmonary Capillary ◽  
Pulmonary Capillary Pressure ◽  
Pulmonary Arterial

We examined the pulmonary vascular response to an intravenous leukotriene D4 (LTD4) injection of (1 microgram X kg-1 X min-1 for 2 min) immediately followed by infusion of 0.133 microgram X kg-1 X min-1 for 15 min in awake sheep prepared with lung lymph fistulas. LTD4 resulted in rapid generation of thromboxane A2 as measured by an increase in plasma thromboxane B2 concentration. The thromboxane B2 generation was associated with increases in pulmonary arterial and pulmonary arterial wedge pressures while left atrial pressure did not change significantly. Pulmonary lymph flow (Qlym) increased (P less than 0.05) transiently from base line 6.87 +/- 1.88 (SE) ml/h to maximum value of 9.77 +/- 1.27 at 15 min following the LTD4 infusion. The maximum increase in Qlym was associated with an increase in the estimated pulmonary capillary pressure. The increase in Qlym was not associated with a change in the lymph-to-plasma protein concentration (L/P) ratio. Thromboxane synthetase inhibition with dazoxiben (an imidazole derivative) prevented thromboxane B2 generation after LTD4 and also prevented the increases in pulmonary vascular pressures and Qlym. We conclude that LTD4 in awake sheep increases resistance of large pulmonary veins. The small transient increase in Qlym can be explained by the increase in pulmonary capillary pressure. Thromboxane appears to mediate both the pulmonary hemodynamic and lymph responses to LTD4 in sheep.

Flow-induced vasodilation in the ferret lung

1997 ◽  
Vol 83 (2) ◽  
pp. 495-502 ◽  
Author(s):  
Joseph H. Chammas ◽  
David. A. Rickaby ◽  
Margarita Guarin ◽  
John H. Linehan ◽  
Christopher C. Hanger ◽  
...  
Keyword(s):  
Shear Stress ◽  
Venous Pressure ◽  
Pulmonary Arteries ◽  
Flow Rates ◽  
Hypoxic Conditions ◽  
Pulmonary Vasodilator ◽  
X Ray Imaging ◽  
Pulmonary Arterial ◽  
Arterial Tone ◽  
Intravascular Pressure

Chammas, Joseph H., David. A. Rickaby, Margarita Guarin, John H. Linehan, Christopher C. Hanger, and Christopher A. Dawson.Flow-induced vasodilation in the ferret lung. J. Appl. Physiol. 83(2): 495–502, 1997.—To examine the possibility that shear stress may be a pulmonary vasodilator stimulus, we studied the effect of changing blood flow on the diameters of small pulmonary arteries in isolated perfused ferret lung lobes. The arteries studied were in the ∼0.3- to 1.3-mm-diameter range, and the diameters were measured by using microfocal X-ray imaging. The diameters were measured at two flow rates, 10 and 40 ml/min, with the intravascular pressure in the measured vessels the same at the two flow rates as the result of venous pressure adjustment. The response to a change in flow was studied under both normoxic and hypoxic conditions. Hypoxia was used to elevate pulmonary arterial tone to increase the likelihood of detecting a vasodilator response. Under normoxic conditions, changing flow had little effect on the arterial diameters, but under hypoxic conditions the arteries were consistently larger at the higher flow than at the lower flow, even though the distending pressure was the same at the two flow rates. The results are consistent with the hypothesis that shear stress is a pulmonary vasodilator stimulus.

scholarly journals Pulmonary hypertension: reasonable selection of specific therapy

2018 ◽  
Vol 15 (1) ◽  
pp. 45-50
Author(s):  
N A Karoli ◽  
S I Sazhnova ◽  
A P Rebrov
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Structural Changes ◽  
Pulmonary Arteries ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial

Pulmonary hypertension is characterized with persistent increase in pulmonary vascular resistance leading to progressive worsening of right ventricular failure and death. The basis for pulmonary arterial hypertension is structural changes in pulmonary arteries and arterioles caused by endothelial dysfunction. Endothelin-1 is the main pathogenic trigger of pulmonary hypertension and potential target for therapeutic exposure. The efficacy of endothelin receptor antagonists is proved in various preclinical and clinical studies. In patients with pulmonary arterial hypertension, the efficacy of dual and selective endothelin receptor antagonists is comparable despite the varied activity against various receptors. Bosentan is the most widely used pulmonary vasodilator which improves exercise tolerance and decelerates disease progression.

Microcirculation Impedance Analysis in Cat Lung

1999 ◽  
Vol 122 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Jian Gao ◽  
Wei Huang ◽  
R. T. Yen
Keyword(s):  
Input Impedance ◽  
Pulmonary Arteries ◽  
Impedance Analysis ◽  
Mean Flow ◽  
Arterial Trunk ◽  
Pulmonary Capillary ◽  
Complete Set ◽  
Pulmonary Arterial ◽  
Pulmonary Microcirculation ◽  
The Impact

An analysis of pulsatile microcirculation in cat lung, with special attention to the pulmonary microvascular impedance, is presented. A theoretical calculation is made on the basis of a complete set of experimental data on the morphology and elasticity of cat’s pulmonary capillary sheets. The transfer matrix of the pulmonary microvascular impedance is obtained. The input impedance at the capillary entrance and exit are determined. The input impedance at the pulmonary arterial trunk is compared under various physiological conditions. It is shown that although the impact of pulmonary microcirculation on the relationship between the steady mean flow and pressure in the pulmonary arteries and veins is decisively large, the influence of the alveolar microcirculation on the input impedance at the pulmonary arterial trunk is small. [S0148-0731(00)01101-8]

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