Antenatal betamethasone therapy augments nitric oxide-mediated relaxation of preterm ovine pulmonary veins

1996 ◽  
Vol 80 (2) ◽  
pp. 390-396 ◽  
Author(s):  
H. Zhou ◽  
Y. Gao ◽  
J. U. Raj
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Isometric Tension ◽  
Glucocorticoid Therapy ◽  
Fourth Generation ◽  
Cyclic Monophosphate ◽  
Significant Difference ◽  
Arteries And Veins

Antenatal glucocorticoid therapy improves pulmonary function in preterm newborns. We have determined the effect of antenatal glucocorticoid therapy on nitric oxide-mediated relaxation in pulmonary vessels of preterm lambs. Ovine fetuses (126 days gestation; full term = 150 days) were injected with betamethasone (0.5 mg/kg body wt) or saline. After 48 h, lambs were delivered, ventilated for 3 h, and killed. Isolated fourth-generation pulmonary arteries (2-3 mm diameter) and veins (1.5-2 mm diameter) were suspended in organ chambers filled with modified Krebs-Ringer solution (95% O2-5% CO2) at 37 degrees C, and their isometric tension was recorded. During contractions to endothelin-1 or U-46619 (in the presence of indomethacin), acetylcholine and bradykinin induced endothelium-dependent nitro-L-arginine-inhibitable relaxation in arteries and veins. The relaxation was greater in veins of betamethasone-treated than in those of control lambs. Veins from lambs without endothelium treated with betamethasone were more sensitive to sodium nitroprusside than veins from controls. For arteries, there was no significant difference in relaxation between different groups. Relaxation induced by 8-bromoguanosine 3′,5′-cyclic monophosphate was similar in arteries and veins of different groups. Radioimmunoassay showed that nitric oxide caused a greater increase in guanosine 3′,5′-cyclic monophosphate in betamethasone-treated veins than in controls. These data suggest that antenatal betamethasone therapy augments nitric oxide-mediated relaxation of pulmonary veins of preterm lambs, probably by increasing soluble guanylate cyclase activity of vascular smooth muscle.

Heterogeneity in role of endothelium-derived NO in pulmonary arteries and veins of full-term fetal lambs

1995 ◽  
Vol 268 (4) ◽  
pp. H1586-H1592 ◽  
Author(s):  
Y. Gao ◽  
H. Zhou ◽  
J. U. Raj
Keyword(s):  
Nitric Oxide ◽  
Isometric Force ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Full Term ◽  
Fourth Generation ◽  
Cyclic Monophosphate ◽  
Arteries And Veins ◽  
Endothelium Dependent Relaxation

Endothelium-derived nitric oxide (EDNO) modulates fetal pulmonary vasoactivity. The role of EDNO in regulation of vasomotor tone in fetal pulmonary arteries vs. that in veins is not known. We have investigated the role of EDNO in the responses of pulmonary arteries and veins of full-term fetal lambs. Fourth-generation pulmonary arterial and venous rings were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2-5% CO2 at 37 degrees C), and their isometric force was measured. N omega-nitro-L-arginine had no effect on the resting tension of pulmonary arteries with endothelium but caused contraction of pulmonary veins with endothelium. The basal level of intracellular guanosine 3',5'-cyclic monophosphate (cGMP) of pulmonary veins with endothelium was higher than that of arteries with endothelium. In pulmonary arteries, bradykinin, but not acetylcholine, induced endothelium-dependent relaxation and an increase in cGMP content. In pulmonary veins, acetylcholine, but not bradykinin, induced endothelium-dependent relaxation and an increase in cGMP content. Agonist-induced maximal relaxation and increases in cGMP content were smaller in pulmonary arteries than in veins. All these endothelium-dependent responses were abolished by N omega-nitro-L-arginine. In tissues without endothelium, nitric oxide induced significantly less relaxation and less increase in cGMP content in pulmonary arteries than in pulmonary veins. All vessels relaxed similarly to 8-bromoguanosine 3',5'-cyclic monophosphate. Our data suggest that the role of EDNO in modulating tone differs between pulmonary arteries and veins in full-term fetal lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Disruption of cGMP production in pulmonary arteries isolated from fetal lambs with pulmonary hypertension

1995 ◽  
Vol 268 (4) ◽  
pp. H1483-H1489 ◽  
Author(s):  
R. H. Steinhorn ◽  
J. A. Russell ◽  
F. C. Morin
Keyword(s):  
Pulmonary Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Ductus Arteriosus ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Fourth Generation ◽  
Response Curves ◽  
Fetal Sheep ◽  
A 23187 ◽  
Arteries And Veins

Ligation of the ductus arteriosus of the fetal sheep produces severe pulmonary hypertension at birth. Standard tissue bath techniques were used to study third- and fourth-generation pulmonary arteries and veins isolated from fetal sheep with pulmonary hypertension created by ligation of the ductus arteriosus 11–12 days before birth as well as from age-matched control sheep. Vessels pretreated with indomethacin and propranolol were submaximally preconstricted with norepinephrine before exposure to A-23187 (10(-8) to 3 x 10(-7) M), sodium nitroprusside (SNP; 10(-9) to 10(-5) M), and nitric oxide (NO) gas (1-973 ppm). Pulmonary veins in both control and ligated animals relaxed similarly and completely to A-23187, SNP, and NO. Control pulmonary arteries relaxed by 16 +/- 2% to A-23187 and relaxed completely to SNP and NO, with concentration-response curves shifted rightward of those observed in pulmonary veins. Pulmonary arteries from ligated animals did not relax at all to A-23187. SNP relaxations in ligated arteries were shifted rightward of control. Ligated arteries relaxed by only 11 +/- 5% to the highest dose of NO. However, control and ligated pulmonary arteries relaxed similarly to 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP; 10(-5) to 10(-3) M) and atrial natriuretic peptide (10(-9) to 10(-7) M). These data are most simply explained by decreased arterial vascular smooth muscle sensitivity to NO at the level of soluble guanylate cyclase.

Prostaglandins E2 and I2 cause greater relaxations in pulmonary veins than in arteries of newborn lambs

1996 ◽  
Vol 81 (6) ◽  
pp. 2534-2539 ◽  
Author(s):  
Yuansheng Gao ◽  
Haiyan Zhou ◽  
Basil O. Ibe ◽  
J. Usha Raj
Keyword(s):  
Adenylate Cyclase ◽  
Isometric Force ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Calcium Ionophore ◽  
Fourth Generation ◽  
Breakdown Product ◽  
Cyclic Monophosphate ◽  
Vasoactive Mediators ◽  
Arteries And Veins

Gao, Yuansheng, Haiyan Zhou, Basil O. Ibe, and J. Usha Raj.Prostaglandins E2 and I2 cause greater relaxations in pulmonary veins than in arteries of newborn lambs. J. Appl. Physiol. 81(6): 2534–2539, 1996.—Prostaglandins E2(PGE2) and I2(PGI2) are important vasoactive mediators in pulmonary vessels. The present study was designed to determine whether the responses of pulmonary arteries to these prostanoids are different from those of veins in newborn lambs. Fourth-generation pulmonary arterial and venous rings without endothelium were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2-5% CO2, 37°C), and their isometric force was measured. During contraction with endothelin-1 or U-46619 (indomethacin was present to eliminate the possible involvement of endogenous cyclooxygenase products), PGE2, PGI2, and carbacyclin (a stable analogue of PGI2) induced greater relaxations in veins than in arteries. In both vessel types, relaxations induced by PGE2 were greater than those induced by PGI2or carbacyclin. Forskolin, an activator of adenylate cyclase, also induced greater relaxation of veins than of arteries. Relaxation induced by 8-bromoadenosine 3′,5′-cyclic monophosphate, an analogue of adenosine 3′,5′-cyclic monophosphate (cAMP), was comparable in both vessel types. Radioimmunoassay revealed that the basal and calcium ionophore A-23187-induced releases of PGE2 or 6-ketoprostaglandin F1α (the stable breakdown product of PGI2) were similar between arteries and veins. Measurement of cAMP (in the presence of isobutylmethylxanthine) showed that PGE2 and forskolin induced greater increase in cAMP in veins than in arteries. Our results demonstrate that PGE2 and PGI2 are more potent vasodilators in pulmonary veins than in arteries in newborn lambs. A difference in the activity of adenylate cyclase may contribute to the differential responses to PGE2 and PGI2 between pulmonary arteries and veins. Furthermore, PGE2appears play an more important role than does PGI2 in modulating pulmonary vascular tone of newborn lambs.

Interaction among ET-1, endothelium-derived nitric oxide, and prostacyclin in pulmonary arteries and veins

1994 ◽  
Vol 267 (1) ◽  
pp. H139-H147 ◽  
Author(s):  
T. M. Zellers ◽  
J. McCormick ◽  
Y. Wu
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Potent Vasoconstrictor ◽  
Eta Receptor Antagonist ◽  
Arteries And Veins

Endothelin-1 causes vasodilation of the intact porcine pulmonary vascular bed. To determine the cause of this vasodilation, we investigated the interactions of endothelin-1 (ET-1), endothelium-derived nitric oxide (EDNO), and prostacyclin in isolated small porcine pulmonary arteries and veins under in vitro conditions. ET-1 caused concentration-dependent contractions in arteries and veins, augmented by the nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine, in pulmonary veins. BQ-123 (ETA-receptor antagonist) depressed the ET-1-induced contractions. Sarafotoxin S6C, an ETB-receptor agonist, caused contractions of pulmonary veins only. Endothelium-dependent relaxations to bradykinin and ET-1 were greater in pulmonary veins compared with arteries, inhibited by N omega-nitro-L-arginine, and reversed by L-arginine. BQ-123 augmented ET-1-induced arterial relaxation. ET-3 and sarafotoxin S6C, ETB-receptor agonists, caused comparable endothelium-dependent relaxations in arteries and veins. ET-1 caused a fourfold greater increase in prostacyclin release in pulmonary veins compared with arteries. We conclude that ET-1 is a potent vasoconstrictor of porcine pulmonary vessels and stimulates the release of EDNO and prostacyclin, which oppose the contractions to the peptide. The release of these endothelium-derived vasodilators appears greater in pulmonary veins.

PAF induces relaxation of pulmonary arteries but contraction of pulmonary veins in the ferret

1995 ◽  
Vol 269 (2) ◽  
pp. H704-H709 ◽  
Author(s):  
Y. Gao ◽  
H. Zhou ◽  
J. U. Raj
Keyword(s):  
Critical Role ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Platelet Activating Factor ◽  
Isometric Tension ◽  
Third Order ◽  
Prostaglandin F2 Alpha ◽  
Pulmonary Arterial ◽  
Arteries And Veins ◽  
Endothelium Dependent Relaxation

The present study was designed to determine whether platelet-activating factor (PAF) has different effects on pulmonary arteries and veins. Third-order pulmonary arterial and venous rings of the ferret were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2-5% CO2, 37 degrees C) and their isometric tension was recorded. Under basal conditions, PAF had no effect on the resting tension of arteries but induced an endothelium-dependent contraction of veins. The contraction was not affected by BW-755C (an inhibitor of cyclooxygenase and lipoxygenase), BQ-123 [an antagonist of endothelin (ET) A (ETA) receptors)], or IRL-1038 (an antagonist of ETB receptors). PAF had no effect on veins during contraction to prostaglandin F2 alpha (PGF 2 alpha) but induced an endothelium-dependent relaxation of arteries. The relaxation was abolished by N omega-nitro-L-arginine. Incubation with PAF for 30 min augmented contractions of veins with endothelium to PGF 2 alpha. The augmentation was not affected by BW-755C, BQ-123, or IRL-1038. Pretreatment with PAF had no effect on the response of veins to phenylephrine or on the response of arteries to either PGF 2 alpha or phenylephrine. These observations demonstrated that, in the ferret, PAF affected differently the response of pulmonary arteries and veins and that the endothelium plays a critical role in the PAF-induced effects. Furthermore, the PAF-induced effects appear not to be mediated by metabolites of arachidonic acid and ET.

Endothelium-dependent relaxations to adenosine in juvenile rabbit pulmonary arteries and veins

1994 ◽  
Vol 266 (5) ◽  
pp. H2001-H2006 ◽  
Author(s):  
R. H. Steinhorn ◽  
F. C. Morin ◽  
D. G. Van Wylen ◽  
S. F. Gugino ◽  
E. C. Giese ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Adenosine Receptor ◽  
Receptor Agonist ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Response Curves ◽  
Pulmonary Vessels ◽  
Oxide Synthase ◽  
Arteries And Veins

We studied the actions of adenosine and its analogues 5'-(N-ethylcarboxamido)-adenosine (NECA) and N6-cyclohexyladenosine (CHA) in pulmonary vessels isolated from juvenile rabbits. Pulmonary arteries relaxed in a concentration-dependent fashion to all three compounds. Pretreatment with the methylxanthine 8-p-sulfophenyltheophylline shifted the concentration-response curves to adenosine and NECA rightward, indicating that the vasodilator effects were mediated by the adenosine receptor. The order of potency of adenosine compounds was NECA > adenosine > CHA, indicating that the A2-receptor mediates relaxations to adenosine in rabbit pulmonary arteries. Endothelium rubbing attenuated relaxations to adenosine at concentrations of < or = 3 x 10(-7) M and to all NECA concentrations. Inhibition of nitric oxide synthase with NG-nitro-L-arginine (L-NNA) similarly attenuated relaxations at concentrations of < or = 3 x 10(-7) M for adenosine and < or = 3 x 10(-8) M for NECA. With the use of the same methods, a substantial endothelial contribution was additionally observed in pulmonary veins to the vasodilator effects of NECA. We conclude that adenosine, and the more specific A2-receptor agonist NECA, dilate pulmonary arteries and veins isolated from young rabbits via a mechanism that is partially dependent on endothelium-derived nitric oxide.

Antenatal betamethasone therapy potentiates nitric oxide-mediated relaxation of preterm ovine coronary arteries

1996 ◽  
Vol 270 (2) ◽  
pp. H538-H544 ◽  
Author(s):  
Y. Gao ◽  
H. Zhou ◽  
J. U. Raj
Keyword(s):  
Nitric Oxide ◽  
Coronary Arteries ◽  
Soluble Guanylate Cyclase ◽  
Calcium Ionophore ◽  
Ringer Solution ◽  
Isometric Tension ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Cyclic Monophosphate ◽  
Endothelium Dependent Relaxation

The present study was designed to test the hypothesis that betamethasone may potentiate nitric oxide-mediated relaxation of coronary arteries of preterm lambs. Isolated coronary arteries were obtained from lambs delivered at 128 days gestation. The lambs were treated intramuscularly with a single dose of betamethasone or saline 48 h before delivery and were killed after 3 h of ventilation after delivery. Vessel rings were suspended in organ chambers filled with modified Krebs-Ringer solution (95% O2-5% CO2, 37 degrees C), and their isometric tension was recorded. The endothelium-dependent relaxation induced by bradykinin and calcium ionophore A23187 was greater in arteries from antenatal betamethasone-treated lambs than in arteries from control lambs. The relaxation was abolished by N omega-nitro-L-arginine. Nitric oxide induced a greater relaxation in vessels from antenatal betamethasone-treated lambs and in vessels preincubated with betamethasone than in vessels from controls. Coronary arteries from control and antenatal betamethasone-treated lambs relaxed similarly to 8-bromoguanosine 3',5'-cyclic monophosphate. Nitric oxide induced a greater increase in guanosine 3',5'-cyclic monophosphate content in coronary arteries from antenatal betamethasone-treated lambs than in arteries from control lambs. Our data suggest that antenatal betamethasone therapy potentiates nitric oxide-mediated relaxation in coronary arteries from preterm lambs, probably by affecting the activity of soluble guanylate cyclase of vascular smooth muscle cells.

Hyporesponsiveness to inhaled nitric oxide in isolated, perfused lungs from endotoxin-challenged rats

1996 ◽  
Vol 271 (6) ◽  
pp. L981-L986 ◽  
Author(s):  
A. Holzmann ◽  
K. D. Bloch ◽  
L. S. Sanchez ◽  
G. Filippov ◽  
W. M. Zapol
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
Sepsis Syndrome ◽  
Inhaled Nitric Oxide ◽  
Pulmonary Vasculature ◽  
Cyclic Monophosphate ◽  
Pulmonary Vasodilation ◽  
Lps Challenge ◽  
And Control ◽  
Selective Pulmonary Vasodilation

Inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in patients with the adult respiratory distress syndrome (ARDS). Approximately 30% of ARDS patients fail to respond to iNO. Because sepsis syndrome often accompanies a decreased response to iNO, we investigated NO responsiveness in isolated, perfused lungs from rats exposed to lipopolysaccharide (LPS). Eighteen hours after intraperitoneal injection of 0.5 mg/kg LPS, rat lungs were isolated, perfused, and preconstricted with U-46619. Ventilation with 0.4, 4, and 40 parts per million by volume NO vasodilated LPS-pretreated lungs 75, 47, and 42% less than control lungs (P < 0.01 value differs at each concentration). The diminished vasodilatory response to iNO was associated with decreased NO-stimulated guanosine 3',5'-cyclic monophosphate (cGMP) release into the perfusate. Soluble guanylate cyclase activity did not differ in lung extracts from LPS-pretreated and control rats. LPS increased pulmonary cGMP-phosphodiesterase (PDE) activity by 40%. The PDE-sensitive cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate vasodilated lungs from LPS-pretreated rats less than lungs from control rats. In contrast, the PDE-insensitive 8-para-chlorophenylthioguanosine 3',5'-cyclic monophosphate vasodilated lungs equally from both groups. After LPS challenge, the rat pulmonary vasculature becomes hyporesponsive to iNO. Hyporesponsiveness to iNO appears partly attributable to increased pulmonary cGMP-PDE activity.

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.

Modulation of vascular tone and reactivity by nitric oxide in porcine pulmonary arteries and veins

2002 ◽  
Vol 174 (1) ◽  
pp. 9-15 ◽  
Author(s):  
M. Bäck ◽  
L. Walch ◽  
X. Norel ◽  
J.-P. Gascard ◽  
G. Mazmanian ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Tone ◽  
Pulmonary Arteries ◽  
Arteries And Veins
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