N omega-nitro-L-arginine attenuates endothelium-dependent pulmonary vasodilation in lambs

1991 ◽  
Vol 260 (4) ◽  
pp. H1299-H1306 ◽  
Author(s):  
J. R. Fineman ◽  
M. A. Heymann ◽  
S. J. Soifer
Keyword(s):  
Arterial Pressure ◽  
Sodium Nitroprusside ◽  
Vascular Tone ◽  
Pulmonary Arterial Pressure ◽  
Competitive Inhibitor ◽  
Pulmonary Vasodilation ◽  
Pulmonary Arterial ◽  
Spontaneously Breathing ◽  
Dose Dependent Increase

To investigate the role of endothelium-derived relaxing factor (EDRF) in the regulation of resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation, we studied the hemodynamic effects of N omega-nitro-L-arginine (a new stereospecific EDRF inhibitor) in 10 spontaneously breathing lambs and then compared the hemodynamic responses to five vasodilators during pulmonary hypertension induced by the infusion of U-46619 (a thromboxane A2 mimetic) or N omega-nitro-L-arginine. N omega-nitro-L-arginine caused a significant dose-dependent increase in pulmonary arterial pressure. Pretreatment with L-arginine blocked this increase, but pretreatment with D-arginine did not, suggesting that N omega-nitro-L-arginine is a competitive inhibitor of L-arginine for EDRF production. During U-46619 infusions, acetylcholine, ATP-MgCl2, isoproterenol, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) decreased pulmonary arterial pressure. During N omega-nitro-L-arginine infusions, the decrease in pulmonary arterial pressure caused by acetylcholine and ATP-MgCl2 (endothelium-dependent vasodilators) was significantly attenuated, but the decrease caused by isoproterenol, sodium nitroprusside, and 8-bromo-cGMP (endothelium-independent vasodilators) was unchanged. This study supports the hypothesis that EDRF in part mediates resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation. N omega-nitro-L-arginine is useful for studying EDRF inhibition in intact animals.

In vivo attenuation of endothelium-dependent pulmonary vasodilation by methylene blue

1991 ◽  
Vol 71 (2) ◽  
pp. 735-741 ◽  
Author(s):  
J. R. Fineman ◽  
M. R. Crowley ◽  
M. A. Heymann ◽  
S. J. Soifer
Keyword(s):  
Methylene Blue ◽  
Smooth Muscle ◽  
Arterial Pressure ◽  
Guanylate Cyclase ◽  
Vascular Tone ◽  
Pulmonary Arterial Pressure ◽  
Pulmonary Vasodilation ◽  
Pulmonary Arterial

In vitro evidence suggests that resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation are mediated by changes in vascular smooth muscle concentrations of guanosine 3′,5′-cyclic monophosphate (cGMP). We investigated this hypothesis in vivo in 19 mechanically ventilated intact lambs by determining the hemodynamic effects of methylene blue (a guanylate cyclase inhibitor) and then by comparing the hemodynamic response to five vasodilators during pulmonary hypertension induced by the infusion of U-46619 (a thromboxane A2 mimic) or methylene blue. Methylene blue caused a significant time-dependent increase in pulmonary arterial pressure. During U-46619 infusions, acetylcholine, ATP-MgCl2, sodium nitroprusside, isoproterenol, and 8-bromo-cGMP decreased pulmonary arterial pressure. During methylene blue infusions, the decreases in pulmonary arterial pressure caused by acetylcholine and ATP-MgCl2 (endothelium-dependent vasodilators) and sodium nitroprusside (an endothelium-independent guanylate cyclase-dependent vasodilator) were attenuated by greater than 50%. The decreases in pulmonary arterial pressure caused by isoproterenol and 8-bromo-cGMP (endothelium-independent vasodilators) were unchanged. This study in intact lambs supports the in vitro evidence that changes in vascular smooth muscle cell concentrations of cGMP in part mediate resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation.

L-Arginine, a precursor of EDRF in vitro, produces pulmonary vasodilation in lambs

1991 ◽  
Vol 261 (5) ◽  
pp. H1563-H1569 ◽  
Author(s):  
J. R. Fineman ◽  
R. Chang ◽  
S. J. Soifer
Keyword(s):  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Phosphodiesterase Inhibitor ◽  
Hemodynamic Effects ◽  
Synthesis Inhibitor ◽  
Pulmonary Vasodilation ◽  
Pulmonary Arterial ◽  
Rate Limiting

There is increasing evidence that resting pulmonary vascular tone is mediated in part by the release of endothelium-derived relaxing factors (EDRF). Because L-arginine may be a precursor for EDRF synthesis, we studied the pulmonary vasodilating effects of L-arginine at rest and during pulmonary hypertension in 16 intact newborn lambs. At rest, the intravenous infusions of L-arginine (150 mg/kg) had no hemodynamic effects. However, during pulmonary hypertension induced by hypoxia or the infusion of U-46619 (a thromboxane A2 mimic), L-arginine decreased pulmonary arterial pressure by 22 and 27%, respectively (P less than 0.05). The decrease in pulmonary arterial pressure produced by L-arginine was blocked by methylene blue, a guanylate cyclase inhibitor, and augmented by Zapranast, a guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor (-17.9 vs. -31.2%, P less than 0.05). In addition, L-arginine partially reversed the pulmonary hypertension induced by N omega-nitro-L-arginine, a competitive EDRF synthesis inhibitor, but D-arginine had no hemodynamic effects. This study suggests that L-arginine produces pulmonary vasodilation by increasing cGMP concentrations, supporting the in vitro hypothesis that L-arginine is a precursor for EDRF synthesis, whose availability may become rate limiting during pulmonary hypertension.

Pulmonary vasodilation to adrenomedullin: a novel peptide in humans

1995 ◽  
Vol 268 (6) ◽  
pp. H2211-H2215 ◽  
Author(s):  
J. Heaton ◽  
B. Lin ◽  
J. K. Chang ◽  
S. Steinberg ◽  
A. Hyman ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Vasomotor Tone ◽  
Pulmonary Vasodilation ◽  
Vascular Bed ◽  
Pulmonary Vasodilator ◽  
Vasodilator Activity ◽  
Pulmonary Arterial ◽  
Cgrp Receptor Antagonist ◽  
Pulmonary Vascular Bed

The present study investigates the effects of human adrenomedullin (ADM) on the pulmonary vascular bed of isolated, blood-perfused rat lung. Because pulmonary blood flow and left atrial pressure were constant, changes in pulmonary arterial pressure directly reflect changes in pulmonary vascular resistance. Under conditions of resting (low) pulmonary vasomotor tone, intra-arterial bolus injections of ADM-(1-52) and two truncated sequences of ADM-(1-52) [ADM-(1-12) and ADM-(13-52)] did not alter pulmonary arterial pressure. When pulmonary vasomotor tone was increased by U-46619, a thromboxane A2 mimic, intra-arterial bolus injections of ADM-(1-52) and ADM-(13-52) at similar doses produced similar, dose-dependent reductions in pulmonary arterial pressure. On a molar basis, ADM-(1-52) had greater pulmonary vasodilator activity than isoproterenol. In contrast, ADM-(1-12) had no activity. When pulmonary vasomotor tone was actively increased to the same level using KCl, the pulmonary vasodilator activity of ADM-(13-52) was decreased 10-fold. The present data demonstrate that ADM-(1-52) dilates the pulmonary vascular bed and suggest that the pulmonary vasodilator activity of ADM is greater on pulmonary blood vessels preconstricted through a receptor-dependent mechanism. Because meclofenamate, nitro-L-arginine methyl ester, methysergide, BW A-1433U83, U-37883A, and calcitonin gene-related peptide [CGRP-(8-37)], a CGRP-receptor antagonist, did not alter the pulmonary vasodilator response to ADM-(1-52), the present data suggest that ADM dilates the pulmonary vascular bed independently of cyclooxygenase products, endothelium-derived relaxation factor, serotoninergic receptors, adenosine1 purinoreceptors, ATP-dependent potassium channels, and CGRP receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclooxygenase inhibition prevents PMA-induced increases in lung vascular permeability

1990 ◽  
Vol 69 (4) ◽  
pp. 1494-1501 ◽  
Author(s):  
P. B. Zanaboni ◽  
J. D. Bradley ◽  
L. J. Baudendistel ◽  
R. O. Webster ◽  
T. E. Dahms
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Vascular Occlusion ◽  
Fluid Filtration ◽  
Cyclooxygenase Inhibition ◽  
Pulmonary Arterial ◽  
Permeability Increase ◽  
Txa2 Receptor Antagonist ◽  
Synthase Inhibitor

The effect of cyclooxygenase inhibition in phorbol myristate acetate (PMA)-induced acute lung injury was studied in isolated constant-flow blood-perfused rabbit lungs. PMA caused a 51% increase in pulmonary arterial pressure (localized in the arterial and middle segments as measured by vascular occlusion pressures), a 71% increase in microvascular permeability (measured by the microvascular fluid filtration coefficient, Kf), and a nearly threefold increase in perfusate thromboxane (Tx) B2 levels. Cyclooxygenase inhibition with three chemically dissimilar inhibitors, indomethacin (10(-7) and 10(-6) M), meclofenamate (10(-6) M), and ibuprofen (10(-5) M), prevented the Kf increase without affecting the pulmonary arterial pressure increase or resistance distribution changes after PMA administration. The specific role of TxA2 was investigated by pretreatment with OKY-046, a specific Tx synthase inhibitor, or infusion of SQ 29548, a TxA2 receptor antagonist; both compounds failed to protect against either the PMA-induced permeability or the vascular resistance increase. These results indicate that cyclooxygenase-mediated products of arachidonic acid other than TxA2 mediate the PMA-induced permeability increase but not the hypertension.

Low exercise pulmonary resistance is not dependent on vasodilator prostaglandins

1983 ◽  
Vol 55 (2) ◽  
pp. 558-561 ◽  
Author(s):  
J. Lindenfeld ◽  
J. T. Reeves ◽  
L. D. Horwitz
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Cyclooxygenase Inhibitors ◽  
Pulmonary Resistance ◽  
Before And After ◽  
Pulmonary Arterial

In resting conscious dogs, administration of cyclooxygenase inhibitors results in modest increases in pulmonary arterial pressure and pulmonary vascular resistance, suggesting that vasodilator prostaglandins play a role in maintaining the low vascular resistance in the pulmonary bed. To assess the role of these vasodilator prostaglandins on pulmonary vascular resistance during exercise, we studied seven mongrel dogs at rest and during exercise before and after intravenous meclofenamate (5 mg/kg). Following meclofenamate, pulmonary vascular resistance rose both at rest (250 24 vs. 300 +/- 27 dyn . s . cm-5, P less than 0.01) and with exercise (190 +/- 9 vs. 210 +/- 12 dyn . s . cm-5, P less than 0.05). Systemic vascular resistance rose slightly following meclofenamate both at rest and during exercise. There were no changes in cardiac output. The effects of cyclooxygenase inhibition, although significant, were less during exercise than at rest. This suggests that the normal fall in pulmonary vascular resistance during exercise depends largely on factors other than vasodilator prostaglandins.

M&B 22948, a cGMP phosphodiesterase inhibitor, is a pulmonary vasodilator in lambs

1993 ◽  
Vol 264 (1) ◽  
pp. H252-H258 ◽  
Author(s):  
D. A. Braner ◽  
J. R. Fineman ◽  
R. Chang ◽  
S. J. Soifer
Keyword(s):  
Smooth Muscle ◽  
Arterial Pressure ◽  
Smooth Muscle Cell ◽  
Vascular Tone ◽  
Pulmonary Arterial Pressure ◽  
Cell Concentration ◽  
Phosphodiesterase Inhibitor ◽  
Relaxing Factor ◽  
Pulmonary Arterial ◽  
Endothelium Derived Relaxing Factor

To investigate the hypothesis that pulmonary vascular tone and endothelium-dependent pulmonary vasodilation are mediated by changes in the vascular smooth muscle cell concentration of cGMP, we studied the hemodynamic effects of M&B 22948, a selective guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor, in eight intact newborn lambs. At rest, M&B 22948 (1.0-2.5 mg/kg) selectively decreased pulmonary arterial pressure (by 8.5 +/- 6.6 to 10.3 +/- 4.5%, P < 0.05). Similarly, M&B 22948 (0.5-5.0 mg/kg) produced selective dose-dependent decreases in pulmonary arterial pressure during pulmonary hypertension induced either by U46619 (by 7.7 +/- 4.2 to 44.2 +/- 4.4%, P < 0.05) or by alveolar hypoxia (by 9.5 +/- 6.2 to 29.0 +/- 11.0%, P < 0.05). In addition, M&B 22948 augmented the pulmonary vasodilating effects of acetylcholine and ATP (both endothelium- and cGMP-dependent vasodilators) but not isoproterenol (an endothelium-independent and cAMP-dependent vasodilator). Because M&B 22948 inhibits the breakdown of cGMP, this study supports the in vitro data that changes in the vascular smooth muscle cell concentration of cGMP, in part, may regulate pulmonary vascular tone and mediate endothelium-dependent vasodilator responses in the pulmonary circulation. In addition, N omega-nitro-L-arginine (an inhibitor of endothelium-derived relaxing factor synthesis) blocked the vasodilating effects of M&B 22948, suggesting that the majority of endogenous cGMP is generated by the release of endothelium-derived relaxing factor.

scholarly journals Identification of the molecular mechanisms underlying brisket disease in Holstein heifers via microbiota and metabolome analyses

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kun Yao ◽  
Shuxiang Wang ◽  
Naren Gaowa ◽  
Shuai Huang ◽  
Shengli Li ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Molecular Mechanisms ◽  
Pulmonary Arterial Pressure ◽  
Economic Loss ◽  
Blood Oxygen Saturation ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial ◽  
The Mean ◽  
Low Levels

AbstractBrisket disease (BD) is common among Holstein heifers in high-altitude environments, and this disease may result in serious economic loss. At present, no effective treatment is available for brisket disease. In this study, liver and cecum samples were collected from five heifers with BD and five healthy heifers (HH) for analyses of the metabolome and microbiota. The mean pulmonary arterial pressure and systolic blood pressure were significantly higher in BD heifers, whereas the average breathing rate, blood oxygen saturation, and glucose level were significantly lower in BD group than in the HH group. Further, 16S rDNA data showed that the abundance of Firmicutes was significantly lower and that of Bacteroidetes was significantly higher in BD group than in the HH group. At the genus level, the BD group heifers harbored fewer Ruminococcaceae and Lachnospiraceae than the HH group. Several metabolites, including beta-d-fructose, d-ribose, 1,4-beta-d-glucan, sucrose, and glucose-6-phosphate were present at low levels in BD heifers. Moreover, the mean pulmonary arterial pressure was negatively correlated with beta-d-fructose (r =  − 0.74; P = 0.013), d-ribose (r =  − 0.72; P = 0.018), and acetyl-tyrosine-ethyl-ester (r =  − 0.71; P = 0.022). We also found that mean pulmonary arterial pressure was negatively correlated with most of the genera, including those in the families of Lachnospiraceae and Ruminococcaceae. In summary, the decreased levels of metabolites and microbial genera might affect BD by limiting the energy supply. This study may help us better understand the role of the microbiota in BD and provide new insights into the management of feeding to decrease the rate of BD in Holstein dairy cows in the Qinghai-Tibetan plateau.

scholarly journals Role of Endothelin-1 Receptor Antagonist in Reducing Perioperative Pulmonary Arterial Hypertension after Surgical Correction of Ventricular Septal Defect

2016 ◽  
Vol 9 (1) ◽  
pp. 55-59
Author(s):  
Rampada Sarker ◽  
ASMS Islam ◽  
SC Mandal ◽  
Kazi Abul Hasan ◽  
Manoz Kumar Sarker ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Ventricular Septal Defect ◽  
Arterial Pressure ◽  
Arterial Hypertension ◽  
Septal Defect ◽  
Pulmonary Arterial Pressure ◽  
Surgical Correction ◽  
Endothelin 1 ◽  
Pulmonary Arterial

Background: This study was designed to determine the role of oral ambrisentan, an endothelin-1 receptor, in reducing perioperative pulmonary arterial hypertension during surgical correction of ventricular septal defect.Methods: This study was carried out among 54 patients of ventricular septal defect with pulmonary arterial hypertension undergoing surgical correction. The patients were divided into two groups; study group received oral ambrisentan, an endothelin-1 receptor antagonist peri-operatively, starting one week before surgery. Pulmonary arterial pressure was measured by echocardiography, cardiac catheterization and directly from pulmonary artery during surgical procedure.Results: Pulmonary arterial pressure was reduced significantly in the group in which oral amrisentan was given perioperatively. There was further reduction of pulmonary arterial pressure at discharge from hospital and at one month follow-up.Conclusion: Oral ambrisentan can reduce pulmonary arterial pressure perioperatively in patients underwent surgical correction of ventricular septal defect.Cardiovasc. j. 2016; 9(1): 55-59

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