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)

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.

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.

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.

Two mechanisms mediate relaxation by bradykinin of pig coronary artery: NO-dependent and -independent responses

1991 ◽  
Vol 261 (3) ◽  
pp. H830-H835 ◽  
Author(s):  
C. L. Cowan ◽  
R. A. Cohen
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Coronary Artery ◽  
Thromboxane A2 ◽  
Porcine Coronary Artery ◽  
Cyclic Monophosphate ◽  
Pig Coronary Artery ◽  
Endothelium Dependent Relaxation

The role of nitric oxide and guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in the endothelium-dependent relaxation of the porcine coronary artery to bradykinin was investigated by comparing relaxation and cGMP accumulation in the presence or absence of NG-monomethyl-L-arginine (L-NMMA) and methylene blue. Rings were treated with indomethacin to eliminate the effects of prostaglandins. Relaxation to bradykinin of rings contracted with the thromboxane A2 mimetic U-46619 was not affected by L-NMMA and was only minimally inhibited by methylene blue. Rings contracted with elevated potassium (25 mM) also relaxed completely to bradykinin. However, L-NMMA or methylene blue effectively inhibited relaxation to bradykinin in rings contracted with potassium. cGMP accumulation was stimulated by bradykinin and inhibited by L-NMMA or methylene blue in rings contracted with either U-46619 or potassium. These results suggest that in the absence of nitric oxide-induced cGMP accumulation, a nonprostanoid mechanism exists that is capable of completely relaxing U-46619-contracted coronary artery. This mechanism is either inhibited in or unable to relax potassium-contracted rings. These results also demonstrate that nitric oxide mediates the bradykinin-induced cGMP accumulation that is largely responsible for the relaxation during contraction with potassium.

Developmental changes in endothelium-dependent relaxation of pulmonary arteries: role of EDNO and prostanoids

1996 ◽  
Vol 81 (5) ◽  
pp. 2013-2019 ◽  
Author(s):  
Denise C. O’Donnell ◽  
Mary L. Tod ◽  
John B. Gordon
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Arteries ◽  
Calcium Ionophore ◽  
Developmental Changes ◽  
Fourth Generation ◽  
A 23187 ◽  
Age Related ◽  
High Concentrations ◽  
Endothelium Dependent Relaxation

O’Donnell, Denise C., Mary L. Tod, and John B. Gordon.Developmental changes in endothelium-dependent relaxation of pulmonary arteries: role of EDNO and prostanoids. J. Appl. Physiol. 81(5): 2013–2019, 1996.—We hypothesized that maturational changes in both prostaglandin and endothelium-derived nitric oxide (EDNO) activity contribute to developmental changes in endothelium-dependent relaxation of newborn pulmonary arteries. Responses to endothelium-dependent vasodilators acetylcholine, bradykinin, and calcium ionophore A-23187 were determined in phenylephrine-constricted third- and fourth-generation (1- to 2-mm-diameter) pulmonary artery rings from 2-day (2d)- and 1-mo (1m)-old lambs under control conditions (Con), after inhibition of EDNO synthesis with N ω-nitro-l-arginine (l-NNA), after inhibition of prostanoid synthesis with meclofenamate (Mec), or both modulators with both inhibitors. Endothelium-independent responses to sodium nitroprusside (SNP) were also measured in Con rings. Endothelium-dependent relaxation was greater in 2d than 1m Con rings, particularly at high concentrations when an increase in tension occurred in 1m rings. l-NNA attenuated endothelium-dependent relaxation more in 2d rings, and SNP caused greater relaxation in 2d rings. However, Mec abolished all age-related differences by attenuating relaxation in 2d rings and constriction in 1m rings. These data suggest that developmental changes in endothelium-dependent responses of ovine pulmonary artery rings reflect both a decrease in EDNO activity and maturational differences in the relative influence of dilator and constrictor prostanoids.

scholarly journals Role of protein kinase G in nitric oxide- and cGMP-induced relaxation of newborn ovine pulmonary veins

1999 ◽  
Vol 87 (3) ◽  
pp. 993-998 ◽  
Author(s):  
Yuansheng Gao ◽  
Srinivas Dhanakoti ◽  
Jean-Francois Tolsa ◽  
J. Usha Raj
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Biochemical Study ◽  
Critical Role ◽  
Pulmonary Veins ◽  
Protein Kinase G ◽  
Fourth Generation ◽  
Cgmp Analog ◽  
A Cell

In a variety of systemic blood vessels, protein kinase G (PKG) plays a critical role in mediating relaxation induced by agents that elevate cGMP, such as nitric oxide. The role of PKG in nitric oxide- and cGMP-induced relaxation is less certain in the pulmonary circulation. In the present study, we examined the effects of inhibitors of PKG on the responses of isolated fourth-generation pulmonary veins of newborn lambs (10 ± 1 days of age) to nitric oxide and cGMP. In vessels preconstricted with endothelin-1, nitric oxide and 8-bromo-cGMP (a cell-membrane-permeable cGMP analog) induced concentration-dependent relaxation. The relaxation was significantly attenuated by β-phenyl-1, N 2-etheno-8-bromoguanosine-3′,5′-cyclic monophosphorothionate (Rp-8-Br-PET-cGMPS; a PKG inhibitor) and N-[2-(methylamino)ethyl]5-isoquinolinesulfonamide [H-8; an inhibitor of PKG and protein kinase A (PKA)] but was not affected by KT-5720 (a PKA inhibitor). Biochemical study showed that PKG activity in newborn ovine pulmonary veins was inhibited by 8-Br-PET-cGMPS and H-8 but not by KT-5720. PKA activity was not affected by 8-Br-PET-cGMPS but was inhibited by H-8 and KT-5720. These results suggest that PKG is involved in relaxation of pulmonary veins of newborn lambs induced by nitric oxide and cGMP.

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.

Effect of L-NAME on pressure-flow relationships in isolated rabbit lungs: role of red blood cells

1995 ◽  
Vol 269 (6) ◽  
pp. H1941-H1948 ◽  
Author(s):  
R. S. Sprague ◽  
A. H. Stephenson ◽  
R. A. Dimmitt ◽  
N. L. Weintraub ◽  
C. A. Branch ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Red Blood Cells ◽  
Salt Solution ◽  
Blood Cells ◽  
Pulmonary Arteries ◽  
Physiological Salt Solution ◽  
Rabbit Lung ◽  
Pressure Flow ◽  
Arteries And Veins

Nitric oxide (NO) is produced by and relaxes pulmonary arteries and veins; however, a role for NO as a participant in the control of pulmonary vascular resistance (PVR) remains to be defined. Here we investigated the hypothesis that for NO to serve as a determinant of PVR in the rabbit requires the presence of blood. In isolated blood-perfused rabbit lungs, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) increased PVR and the slope of the pressure-flow relationship. These effects of L-NAME were prevented by pretreatment with L-arginine. In contrast, in lungs perfused with a physiological salt solution, L-NAME had no effect on PVR or the pressure-flow relationship. The addition of washed red blood cells (RBCs) to physiological salt solution, but not the addition of plasma and platelets, restored the response to L-NAME. This effect of RBCs was not reproduced by increasing perfusate viscosity with dextran. These results suggest that, in the rabbit lung, NO is a determinant of PVR in the presence of blood. Moreover, that aspect of blood that permits the generation of NO appears to be related to the RBC and not to perfusate viscosity.

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.

Modulatory role of EDRF in hypoxic contraction of isolated porcine pulmonary arteries

1992 ◽  
Vol 262 (3) ◽  
pp. H691-H697 ◽  
Author(s):  
M. Ogata ◽  
M. Ohe ◽  
D. Katayose ◽  
T. Takishima
Keyword(s):  
Contractile Response ◽  
Isometric Force ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Pulmonary Vasoconstriction ◽  
Basal Release ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation ◽  
Porcine Pulmonary Artery

To examine the hypothesis that suppression of basal release of endothelium-derived relaxing factor (EDRF) by hypoxia might be related to the mechanism of hypoxic pulmonary vasoconstriction, rings of porcine pulmonary artery (PA, 2 mm OD) were suspended in organ chambers and changes in isometric force were measured. Hypoxia significantly reduced endothelium-dependent relaxation induced by acetylcholine and augmented contractile response to phenylephrine. This augmentation by hypoxia was not seen in rings without endothelium. Contractile response to phenylephrine was also enhanced by removal of endothelium. With 15 min of hypoxia, PA contracted and guanosine 3',5'-cyclic monophosphate content decreased. Pretreatment with 10(-6) M methylene blue, 3 x 10(-7) M oxyhemoglobin, and 9.6 x 10(-5) M NG-monomethyl-L-arginine significantly enhanced hypoxic contraction. Furthermore, removal of endothelium also enhanced hypoxic contraction. These results suggest that suppression of basally released EDRF by hypoxia was not the cause of the contractile response to hypoxia and that EDRF modulates the hypoxic contraction of porcine PA in basal conditions at this diameter.

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