Acetylcholine increases pulmonary blood flow in intact fetuses via endothelium-dependent vasodilation

1992 ◽  
Vol 262 (2) ◽  
pp. H406-H410 ◽  
Author(s):  
M. H. Tiktinsky ◽  
J. J. Cummings ◽  
F. C. Morin
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Pulmonary Arterial Pressure ◽  
Control Protocol ◽  
Relaxing Factor ◽  
Fetal Lamb ◽  
Pulmonary Arterial ◽  
Endothelium Derived Relaxing Factor ◽  
Near Term

In vitro, acetylcholine causes vasodilation by releasing endothelium-derived relaxing factor (EDRF) from endothelial cells. EDRF may be nitric oxide, derived from the amino acid L-arginine (L-Arg), by a process that is inhibited by NG-monomethyl-L-arginine (L-NMMA) and restored by L-Arg. We studied the effect of L-NMMA and L-Arg on the increase in pulmonary blood flow caused by acetylcholine in unanesthetized intrauterine near-term fetal lambs. Three protocols were employed. In each protocol, acetylcholine (0.48 +/- 0.15 micrograms/kg) was injected at 15-min intervals for 120 min. In the control protocol, nothing else was given. In the second protocol, L-NMMA (14 +/- 5 mg/kg) was given at 35 min. In the third protocol, L-NMMA was given at 35 min followed by L-Arg (138 +/- 73 mg/kg) at 80 min. In the control protocol, acetylcholine increased pulmonary blood flow 179 +/- 17% while it decreased pulmonary arterial pressure 15 +/- 1% and did not affect left atrial pressure. The response to each injection lasted less than 1 min and did not change throughout the experiment. L-NMMA completely blocked, whereas L-Arg completely restored, the effect of acetylcholine on pulmonary blood flow. We conclude that acetylcholine increases pulmonary blood flow in the fetal lamb via the release of EDRF derived from L-Arg. We speculate that endothelium-dependent vasodilation may play a role in the increase in pulmonary blood flow at birth.

Increasing oxygen tension dilates fetal pulmonary circulation via endothelium-derived relaxing factor

1993 ◽  
Vol 265 (1) ◽  
pp. H376-H380 ◽  
Author(s):  
M. H. Tiktinsky ◽  
F. C. Morin
Keyword(s):  
Blood Flow ◽  
Oxygen Tension ◽  
Hyperbaric Oxygen ◽  
Pulmonary Circulation ◽  
Left Atrial ◽  
Pulmonary Blood Flow ◽  
Absolute Pressure ◽  
Relaxing Factor ◽  
Pulmonary Arterial ◽  
Endothelium Derived Relaxing Factor

We examined the role of endothelium-derived relaxing factor (EDRF) in the increase in pulmonary blood flow caused by increasing oxygen tension in the lungs of the fetus. Fetal lambs at 133 days of gestation were instrumented for intrauterine measurement of pulmonary arterial, left atrial, and amniotic fluid pressure and pulmonary blood flow. Three days later oxygen tension in the pulmonary arterial blood of the fetus was doubled by having the ewe breathe 100% oxygen at 3 atm absolute pressure. In the control fetuses (n = 5), hyperbaric oxygenation increased pulmonary blood flow eightfold. Blocking EDRF production by infusing 45 mg of NG-monomethyl-L-arginine into the superior vena cava of the fetus over 5 min starting 30 min after the beginning of hyperbaric oxygen reversed the increase in pulmonary blood flow (n = 5). Blocking EDRF production by infusing NG-nitro-L-arginine at 1 mg/min for 60 min starting 30 min before hyperbaric oxygen blunted the initial increase in pulmonary blood flow and eliminated it by the end of the experiment (n = 5). As hyperbaric oxygen did not significantly alter pulmonary arterial or left atrial pressure, changes in pulmonary vascular conductance paralleled those in pulmonary blood flow. We conclude that the majority of the vasodilation of the fetal pulmonary circulation caused by increasing oxygen tension is mediated by EDRF. We speculate that EDRF is involved in maintaining low vascular tone at the relatively high oxygen tension of the postnatal lung.

Regional pulmonary blood flow during 96 hours of hypoxia in conscious sheep

1986 ◽  
Vol 61 (6) ◽  
pp. 2136-2143 ◽  
Author(s):  
D. C. Curran-Everett ◽  
K. McAndrews ◽  
J. A. Krasney
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Pulmonary Blood Flow ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Superior Vena ◽  
Acute Hypoxia ◽  
Vena Cava ◽  
Normobaric Hypoxia ◽  
Pulmonary Arterial

The effects of acute hypoxia on regional pulmonary perfusion have been studied previously in anesthetized, artificially ventilated sheep (J. Appl. Physiol. 56: 338–342, 1984). That study indicated that a rise in pulmonary arterial pressure was associated with a shift of pulmonary blood flow toward dorsal (nondependent) areas of the lung. This study examined the relationship between the pulmonary arterial pressor response and regional pulmonary blood flow in five conscious, standing ewes during 96 h of normobaric hypoxia. The sheep were made hypoxic by N2 dilution in an environmental chamber [arterial O2 tension (PaO2) = 37–42 Torr, arterial CO2 tension (PaCO2) = 25–30 Torr]. Regional pulmonary blood flow was calculated by injecting 15-micron radiolabeled microspheres into the superior vena cava during normoxia and at 24-h intervals of hypoxia. Pulmonary arterial pressure increased from 12 Torr during normoxia to 19–22 Torr throughout hypoxia (alpha less than 0.049). Pulmonary blood flow, expressed as %QCO or ml X min-1 X g-1, did not shift among dorsal and ventral regions during hypoxia (alpha greater than 0.25); nor were there interlobar shifts of blood flow (alpha greater than 0.10). These data suggest that conscious, standing sheep do not demonstrate a shift in pulmonary blood flow during 96 h of normobaric hypoxia even though pulmonary arterial pressure rises 7–10 Torr. We question whether global hypoxic pulmonary vasoconstriction is, by itself, beneficial to the sheep.

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 Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth

1990 ◽  
Vol 259 (6) ◽  
pp. H1921-H1927 ◽  
Author(s):  
S. H. Abman ◽  
B. A. Chatfield ◽  
S. L. Hall ◽  
I. F. McMurtry
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Circulation ◽  
Atrial Natriuretic Factor ◽  
Pulmonary Blood Flow ◽  
Relaxing Factor ◽  
Natriuretic Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Atrial Natriuretic

To examine the potential role of endothelium-derived relaxing factor (EDRF) in regulation of the perinatal pulmonary circulation, we studied the hemodynamic effects of a selective inhibitor of EDRF production, nitro-L-arginine (L-NA), on pulmonary vascular tone and dilator reactivity in the late-gestation ovine fetus and on the pulmonary vasodilation that normally occurs at birth. L-NA infusion decreased pulmonary blood flow from 78 +/- 8 to 65 +/- 6 ml/min (P less than 0.01) and increased pulmonary artery pressure from 48 +/- 2 to 54 +/- 3 mmHg (P less than 0.002, n = 8 animals). To study the selectivity of L-NA on vasodilator responses to endothelium-dependent (acetylcholine) and -independent (atrial natriuretic factor) stimuli, we measured responses to brief infusions of each dilator before and after L-NA treatment. Acetylcholine increased pulmonary blood flow during the control period but not after L-NA treatment. In contrast, L-NA had little effect on the vasodilator response to atrial natriuretic factor. To study the role of EDRF in the transition of the pulmonary circulation from fetal to neonatal conditions, we infused L-NA into the left pulmonary artery immediately before cesarean-section delivery. In comparison with control animals, the rise in pulmonary blood flow at 1 h after delivery was reduced in the L-NA-treated animals (331 +/- 28 in control vs. 185 +/- 16 ml/min in treated, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Major contribution of central pulmonary reservoir discharge to increased pulmonary arterial diastolic blood flow after birth in near-term lambs

2016 ◽  
Vol 311 (4) ◽  
pp. R702-R709 ◽  
Author(s):  
Joseph J. Smolich ◽  
Jonathan P. Mynard
Keyword(s):  
Blood Flow ◽  
Left Atrial ◽  
Pulmonary Trunk ◽  
Pulmonary Perfusion ◽  
Flow Profile ◽  
Cesarean Section Delivery ◽  
Time Flow ◽  
Fetal Lamb ◽  
Pulmonary Arterial ◽  
Near Term

Recent fetal lamb data have suggested that the pulmonary trunk (PT) region displays a reservoir function and that a pharmacologically induced fall in pulmonary vascular resistance (PVR) increases and redistributes diastolic discharge from this central pulmonary reservoir toward the lungs, thereby producing a positive diastolic offset in the pulmonary arterial (PA) blood flow profile. As a similar offset in PA flow characteristically occurs after birth, this study tested the hypotheses that 1) central pulmonary reservoir discharge is both redistributed toward the lungs and increased in magnitude during the birth transition and 2) discharge from this reservoir constitutes a major component of increased PA diastolic blood flow after birth. Six anesthetized near-term fetal lambs were instrumented with PT, ductal and left PA transit-time flow probes, and aortic, PT and left atrial catheters. Hemodynamic data were recorded in fetuses and at regular intervals during 2-h mechanical ventilation following cesarean section delivery. Diastolic PA blood flow rose from near zero in fetuses to 468 ± 188 ml/min by 15 min ( P < 0.001). Central pulmonary reservoir discharge in fetuses (99 ± 44 ml/min) passed primarily right-to-left across the ductus. However, this reservoir discharge redistributed entirely to the lungs by 1 min after birth, and then doubled to a peak of 214 ± 167 ml/min at 15 min ( P < 0.001). Reservoir discharge subsequently stabilized at 151 ± 60 ml/min at 30–120 min, which comprised ∼50% of diastolic and ∼20% of mean PA blood flow. These findings suggest that enhanced diastolic central pulmonary reservoir discharge plays a major role in supporting an increased pulmonary perfusion after birth.

Development of pulmonary vascular response to oxygen

1988 ◽  
Vol 254 (3) ◽  
pp. H542-H546 ◽  
Author(s):  
F. C. Morin ◽  
E. A. Egan ◽  
W. Ferguson ◽  
C. E. Lundgren
Keyword(s):  
Blood Flow ◽  
Right Ventricular ◽  
Oxygen Tension ◽  
Pulmonary Circulation ◽  
Pulmonary Blood Flow ◽  
Arterial Oxygen Tension ◽  
Arterial Oxygen ◽  
Absolute Pressure ◽  
Fetal Lamb ◽  
Near Term

The ability of the pulmonary circulation of the fetal lamb to respond to a rise in oxygen tension was studied from 94 to 146 days of gestation. The unanesthetized ewe breathed room air at normal atmospheric pressure, followed by 100% oxygen at three atmospheres absolute pressure in a hyperbaric chamber. In eleven near-term lambs (132 to 146 days of gestation), fetal arterial oxygen tension (PaO2) increased from 25 +/- 1 to 55 +/- 6 Torr (mean +/- SE), which increased the proportion of right ventricular output distributed to the fetal lungs from 8 +/- 1 to 59 +/- 5%. In five very immature lambs (94 to 101 days of gestation), fetal PaO2 increased from 27 +/- 1 to 174 +/- 70 Torr, but the proportion of right ventricular output distributed to the lung did not change, 8 +/- 1 to 9 +/- 1%. In five of the near-term lambs, pulmonary blood flow was measured. It increased from 34 +/- 3 to 298 +/- 35 ml.kg fetal wt-1.min-1, an 8.8-fold increase. We conclude that the pulmonary circulation of the fetal lamb does not respond to an increase in oxygen tension before 101 days of gestation; however, near term an increase in oxygen tension alone can induce the entire increase in pulmonary blood flow that normally occurs after the onset of breathing at birth.

Effects of blood flow on lung ACE kinetics: evidence for microvascular recruitment

1991 ◽  
Vol 71 (6) ◽  
pp. 2244-2254 ◽  
Author(s):  
H. J. Toivonen ◽  
J. D. Catravas
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Pulmonary Arterial Pressure ◽  
Left Lung ◽  
In Vivo Assays ◽  
Vascular Bed ◽  
Pulmonary Arterial ◽  
Microvascular Recruitment ◽  
The Relationship

The parameter Amax/Km (product of reactant enzyme mass in perfused microvessels and the constant kcat/Km), calculated from in vivo assays of pulmonary endothelial ectoenzymes (e.g., angiotensin-converting enzyme, ACE), can provide estimates of the perfused pulmonary microvascular surface area (PMSA) in the absence of enzyme dysfunction. We examined the relationship between PMSA and pulmonary blood flow (Qb) in anesthetized rabbits placed on total heart bypass, using [3H]benzoyl-Phe-Ala-Pro (BPAP) as the ACE substrate. When Qb was increased from 250 to 1,100 ml/min, at zone 3 conditions, pulmonary arterial pressure increased, pulmonary vascular resistance (PVR) decreased, and Amax/Km increased linearly, reflecting increasing PMSA. When only the left lung was perfused, increasing Qb from 250 to 636 +/- 17 ml/min (the last value representing fully recruited and/or distended vascular bed), PVR decreased, while Amax/Km increased. When Qb was further increased to 791 +/- 44 ml/min, both PVR and Amax/Km remained unchanged, confirming the lack of additional changes in PMSA. We conclude that Amax/Km provides a sensitive indication of PMSA, because it 1) increases with increasing Qb and decreasing PVR, 2) reaches a maximum at Qb values that correspond to the minimal values in PVR, and 3) like PVR, did not change with further increases in Qb. Compared with predicted changes in PMSA produced by either microvascular recruitment alone or distension alone, our data indicate that recruitment is a larger contributor to the observed increase in PMSA.

Pulmonary venular responses to anoxia, 5-hydroxytryptamine and histamine

1960 ◽  
Vol 198 (5) ◽  
pp. 1032-1036 ◽  
Author(s):  
Domingo M. Aviado
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Pulmonary Blood Flow ◽  
Pulmonary Arterial Pressure ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial ◽  
Constrictor Response

In anesthetized dogs, the inhalation of 5% oxygen causes a rise in pulmonary arterial pressure but no rise in venular pressures measured by catheters with outside diameters of 0.4 mm and 1.0 mm. The venular pressure measured by the 0.4-mm catheter showed a consistent rise to 5-hydroxytryptamine. This venular constrictor response to 5-hydroxytryptamine is encountered even when pulmonary blood flow is kept constant by perfusion. The venular response to histamine is variable.

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