5,6-Epoxyeicosatrienoic acid reduces increases in pulmonary vascular resistance in the dog

1998 ◽  
Vol 275 (1) ◽  
pp. H100-H109 ◽  
Author(s):  
Alan H. Stephenson ◽  
Randy S. Sprague ◽  
Andrew J. Lonigro
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Constant Infusion ◽  
Physiological Salt Solution ◽  
Dependent Manner ◽  
Active Tension ◽  
Epoxyeicosatrienoic Acid ◽  
Vascular Beds ◽  
Venous Segment

We recently reported that canine pulmonary microsomes metabolize arachidonic acid to all four regioisomeric epoxyeicosatrienoic acids (EET). 5,6-EET dilates blood vessels in several nonpulmonary vascular beds, often in a cyclooxygenase-dependent manner. The present study was designed to determine whether 5,6-EET can decrease pulmonary vascular resistance (PVR) in the intact pulmonary circulation. In isolated canine lungs perfused with physiological salt solution, a constant infusion of U-46619 (3.28 ± 0.99 nmol/min) increased PVR 62.1 ± 4.5%. Administration of 5,6-EET (10−5 M) into the perfusate reduced the U-46619-mediated increase in PVR by 23.6 ± 6.1%. These effects of U-46619 and 5,6-EET were limited to changes in resistance solely in the pulmonary venous segment. In contrast, venous as well as arterial segmental resistances were increased in 5-hydroxytryptamine (5-HT)-treated lungs. However, in the latter instance, 5,6-EET reduced arterial but not venous segmental resistance. 5,6-EET increased pulmonary PGI2 synthesis from 70.5 ± 18.4 to 675.9 ± 125.4 ng/min. In the presence of indomethacin (10−4 M), 5,6-EET did not increase PGI2 synthesis nor did it decrease U-46619- or 5-HT-mediated increases in PVR. In canine intrapulmonary vessels, 5,6-EET decreased active tension in veins contracted with U-46619. 5,6-EET decreased active tension in arteries but not veins contracted with 5-HT, consistent with results in the perfused lungs. These results demonstrate that 5,6-EET is a vasodilator in the intact pulmonary circulation. Its dilator activity depends on the constrictor agent present, the segmental resistance, and cyclooxygenase activity.

Selective Pulmonary Vasodilation by Intravenous Infusion of an Ultrashort Half-life Nucleophile/Nitric Oxide Adduct 

1998 ◽  
Vol 88 (1) ◽  
pp. 190-195 ◽  
Author(s):  
Christophe Adrie ◽  
Mona W. Hirani ◽  
Alexandra Holzmann ◽  
Larry Keefer ◽  
Warren M. Zapol ◽  
...  
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Half Life ◽  
Pulmonary Vasculature ◽  
Prostaglandin F2alpha ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasodilator ◽  
Healthy Sheep ◽  
Inhaled No

Background PROLI/NO (C5H7N3O4Na2 x CH3OH) is an ultrashort-acting nucleophile/NO adduct that generates NO (half-life 2 s at 37 degrees C and pH 7.4). Because of its short half-life, the authors hypothesized that intravenous administration of this compound would selectively dilate the pulmonary vasculature but cause little or no systemic hypotension. Methods In eight awake healthy sheep with pulmonary hypertension induced by 9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha, the authors compared PROLI/NO with two reference drugs-inhaled NO, a well-studied selective pulmonary vasodilator, and intravenous sodium nitroprusside (SNP), a nonselective vasodilator. Sheep inhaled 10, 20, 40, and 80 parts per million NO or received intravenous infusions of 0.25, 0.5, 1, 2, and 4 microg x kg-1 x min-1 of SNP or 0.75, 1.5, 3, 6, and 12 microg x kg-1 x min-1 of PROLI/NO. The order of administration of the vasoactive drugs (NO, SNP, PROLI/NO) and their doses were randomized. Results Inhaled NO selectively dilated the pulmonary vasculature. Intravenous SNP induced nonselective vasodilation of the systemic and pulmonary circulation. Intravenous PROLI/NO selectively vasodilated the pulmonary circulation at doses up to 6 microg x kg-1 x min-1, which decreased pulmonary vascular resistance by 63% (P < 0.01) from pulmonary hypertensive baseline values without changing systemic vascular resistance. At 12 microg x kg-1 x min-1, PROLI/NO decreased systemic and pulmonary vascular resistance and pressure. Exhaled NO concentrations were higher during PROLI/NO infusion than during SNP infusion (P < 0.01 with all data pooled). Conclusions The results suggest that PROLI/NO could be a useful intravenous drug to vasodilate the pulmonary circulation selectively.

Effect of high intra-alveolar O2 tensions on pulmonary circulation in perfused lungs of dogs

1965 ◽  
Vol 208 (1) ◽  
pp. 130-138 ◽  
Author(s):  
G. J. A. Cropp
Keyword(s):  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Time Course ◽  
Systemic Circulation ◽  
The Body ◽  
Arterial Blood ◽  
Pulmonary Parenchyma ◽  
Pulmonary Arterial

The resistance to blood flow in the pulmonary circulation of dogs (PVR) increased when their lungs were ventilated with 95–100% oxygen and were perfused with blood that recirculated only through the pulmonary circulation; the systemic circulation was perfused independently. This increase in PVR occurred even when nerves were cut or blocked but was abolished by inhaled isopropylarterenol aerosol. Elevation of intra-alveolar Po2 without increase in pulmonary arterial blood Po2 was sufficient to increase pulmonary vascular resistance. The pulmonary venules or veins were thought to be the likely site of the constriction. These reactions were qualitatively similar to those produced by injection of serotonin or histamine into the pulmonary circulation. The time course of the response and failure to obtain it when the blood was perfused through the remainder of the body before it re-entered the pulmonary circulation are compatible with a theory that high intra-alveolar O2 tension activates a vasoconstrictor material in the pulmonary parenchyma.

Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs

1985 ◽  
Vol 249 (3) ◽  
pp. H570-H576 ◽  
Author(s):  
S. J. Soifer ◽  
R. D. Loitz ◽  
C. Roman ◽  
M. A. Heymann
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Pulmonary Blood Flow ◽  
Blood Gases ◽  
Physiological Control ◽  
Arterial Blood ◽  
High Pulmonary Vascular Resistance

The factors responsible for maintaining the normally low pulmonary blood flow and high pulmonary vascular resistance in the fetus are not well understood. Since leukotrienes are potent pulmonary vasoconstrictors in many adult animal species, we determined whether leukotrienes were perhaps involved in the control of the fetal pulmonary circulation by studying the effects of putative leukotriene end organ antagonists in two groups of fetal lambs. In six fetal lambs studied at 130-134 days gestation, FPL 55712 increased pulmonary blood flow by 61% (P less than 0.05) and reduced pulmonary vascular resistance by 45% (P less than 0.05). There was a small increase in heart rate but no changes in pulmonary and systemic arterial pressures and systemic arterial blood gases. In six other fetal lambs studied at 130-140 days gestation, FPL 57231 increased pulmonary blood flow by 580% (P less than 0.05) and decreased pulmonary vascular resistance by 87% (P less than 0.05). Pulmonary and systemic arterial pressures decreased (P less than 0.05), and heart rate increased (P less than 0.05). Leukotriene end organ antagonism significantly increases fetal pulmonary blood flow and decreases pulmonary vascular resistance. Leukotrienes may play a role in the physiological control of the fetal pulmonary circulation.

Pregnancy blunts pulmonary vascular reactivity in dogs

1980 ◽  
Vol 239 (3) ◽  
pp. H297-H301 ◽  
Author(s):  
L. G. Moore ◽  
J. T. Reeves
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Vascular Reactivity ◽  
Pulmonary Arterial Pressure ◽  
Acute Hypoxia ◽  
Limited Data ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

Pregnancy decreases systemic vascular reactivity but comparatively little is known about the effects of pregnancy on the pulmonary circulation. Pulmonary vascular resistance (PVR) during acute hypoxia was lower (P < 0.01) in eight intact anesthetized pregnant dogs compared to the same animals postpartum. Mean pulmonary arterial pressure (Ppa) and PVR during infusion of prostaglandin (PG) F2 alpha were also reduced during pregnancy. Nonpregnant female dogs (n = 5) treated with estrogen (0.001 mg x kg-1 x da-1) for 2 wk had decreased Ppa (P < 0.01) during acute hypoxia compared to control measurements, but PVR was unchanged during hypoxia and PGF2 alpha infusion. Treatment with progesterone in four dogs had no effect on pulmonary vascular reactivity to hypoxia or PGF2 alpha. Inhibition of circulating PG with meclofenamate in four dogs during pregnancy did not appear to restore pulmonary vascular reactivity. Blunted pulmonary vascular reactivity is suggested by the limited data available for women, but is not seen in pregnant cows. We conclude that pregnancy decreases pulmonary as well as systemic vascular reactivity in the dog, but the mechanism is unclear.

Pulmonary Vascular Effects of Isoflurane Anesthesia after Left Lung Autotransplantation in Chronically Instrumented Dogs

1996 ◽  
Vol 85 (3) ◽  
pp. 592-599. ◽  
Author(s):  
Paul F. Lennon ◽  
Paul A. Murray
Keyword(s):  
Lung Transplantation ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Left Lung ◽  
Pressure Flow ◽  
Isoflurane Anesthesia ◽  
Vasoconstrictor Response ◽  
Chronically Instrumented Dogs ◽  
Conscious Control

Background Single lung transplantation has become a viable therapy for treatment of end-stage pulmonary disease. We previously observed that left lung autotransplantation (LLA) results in a chronic increase in pulmonary vascular resistance and enhanced pulmonary vascular reactivity to sympathetic alpha adrenoreceptor activation. The effects of inhalational anesthetics on the pulmonary circulation after lung transplantation have not been investigated. In the current study, the authors tested the hypothesis that isoflurane anesthesia, known to cause systemic vasodilation, would exert a vasodilator influence on the baseline pulmonary circulation after LLA. In addition, they tested the hypothesis that isoflurane anesthesia, known to attenuate the systemic vasoconstrictor response to sympathetic alpha adrenoreceptor agonists, would reduce the magnitude of the pulmonary vasoconstrictor response to sympathetic alpha adrenoreceptor activation after LLA. Methods Left pulmonary vascular pressure-flow (LPQ) plots were generated in chronically instrumented dogs by measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during inflation of a hydraulic occluder implanted around the right main pulmonary artery. Left pulmonary vascular pressure-flow plots were generated in 8 dogs 2-5 weeks after LLA in the conscious and isoflurane-anesthetized states at baseline, after beta adrenoreceptor block with propranolol, and during the cumulative administration of the alpha agonist, phenylephrine. Left pulmonary vascular pressure-flow plots also were generated in eight conscious, sham-operated control dogs at baseline, after beta block, and during phenylephrine administration. Results Compared with conscious control dogs, LLA resulted in a leftward shift (P &lt; 0.01) in the baseline left pulmonary vascular pressure-flow relation, indicating chronic pulmonary vasoconstriction. Despite the enhanced level of pulmonary vasomotor tone after LLA, isoflurane did not exert a vasodilator influence on the baseline left pulmonary vascular pressure-flow relation. The pulmonary vasoconstrictor response to phenylephrine was enhanced (P &lt; 0.01) after LLA compared with the response measured in conscious control dogs. The magnitude of the pulmonary vasoconstrictor response to phenylephrine after LLA was not attenuated during isoflurane anesthesia. Conclusions Isoflurane anesthesia does not exert a vasodilator influence on the pulmonary circulation in the setting of increased pulmonary vascular resistance after LLA. In addition, in contrast to previous studies of the systemic circulation, isoflurane does not attenuate the enhanced pulmonary vasoconstrictor response to sympathetic alpha adrenoreceptor activation after LLA.

scholarly journals Pulmonary vascular resistance and compliance relationship in pulmonary hypertension

2015 ◽  
Vol 46 (4) ◽  
pp. 1178-1189 ◽  
Author(s):  
Denis Chemla ◽  
Edmund M.T. Lau ◽  
Yves Papelier ◽  
Pierre Attal ◽  
Philippe Hervé
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Arterial Compliance ◽  
Pulmonary Arteries ◽  
Transpulmonary Pressure ◽  
Total Arterial Compliance ◽  
Arterial Load ◽  
Pulmonary Arterial

Right ventricular adaptation to the increased pulmonary arterial load is a key determinant of outcomes in pulmonary hypertension (PH). Pulmonary vascular resistance (PVR) and total arterial compliance (C) quantify resistive and elastic properties of pulmonary arteries that modulate the steady and pulsatile components of pulmonary arterial load, respectively. PVR is commonly calculated as transpulmonary pressure gradient over pulmonary flow and total arterial compliance as stroke volume over pulmonary arterial pulse pressure (SV/PApp). Assuming that there is an inverse, hyperbolic relationship between PVR and C, recent studies have popularised the concept that their product (RC-time of the pulmonary circulation, in seconds) is “constant” in health and diseases. However, emerging evidence suggests that this concept should be challenged, with shortened RC-times documented in post-capillary PH and normotensive subjects. Furthermore, reported RC-times in the literature have consistently demonstrated significant scatter around the mean. In precapillary PH, the true PVR can be overestimated if one uses the standard PVR equation because the zero-flow pressure may be significantly higher than pulmonary arterial wedge pressure. Furthermore, SV/PApp may also overestimate true C. Further studies are needed to clarify some of the inconsistencies of pulmonary RC-time, as this has major implications for our understanding of the arterial load in diseases of the pulmonary circulation.

Ontogeny of NO activity and response to inhaled NO in the developing ovine pulmonary circulation

1994 ◽  
Vol 267 (5) ◽  
pp. H1955-H1961 ◽  
Author(s):  
J. P. Kinsella ◽  
D. D. Ivy ◽  
S. H. Abman
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Hemodynamic Effects ◽  
Fetal Sheep ◽  
Pulmonary Vasodilation ◽  
Ovine Fetus ◽  
Pulmonary Arterial ◽  
Inhaled No

To determine maturation-related changes in nitric oxide (NO) activity in the developing pulmonary circulation, we studied the hemodynamic effects of endogenous NO inhibition under basal conditions in the premature ovine fetus and the response to birth-related stimuli and exogenous NO in 30 fetal sheep at three different gestational ages. At 0.95 term, pulmonary vasodilation during inhaled NO (20 parts per million) was equivalent to the dilator response to 100% O2, but at 0.86 term vasodilation during inhaled NO was greater than the dilator response to 100% O2 (P < 0.05). At 0.78 term, left pulmonary arterial flow (QLPA) did not increase with exposure to either NO or 100% O2. Intrapulmonary infusion of nitro-L-arginine (L-NA) increased basal pulmonary vascular resistance 38% in the premature fetus at 0.78 term. L-NA treatment decreased the ventilation-induced rise in QLPA by 60% compared with controls (P < 0.05). Inhaled NO but not 100% O2 increased QLPA after L-NA treatment to levels achieved with ventilation alone in the controls. We conclude that in the premature pulmonary circulation (0.78 term) 1) basal pulmonary vascular resistance is modulated by endogenous NO, 2) pulmonary vasodilation at birth is partly mediated by endogenous NO activity, and 3) inhaled NO causes potent vasodilation.

Abnormal responses to pulmonary vasodilators in conscious dogs after left lung autotransplantation

1993 ◽  
Vol 264 (3) ◽  
pp. H917-H925 ◽  
Author(s):  
K. Nishiwaki ◽  
D. P. Nyhan ◽  
R. S. Stuart ◽  
P. Rock ◽  
P. M. Desai ◽  
...  
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Left Lung ◽  
Conscious Dogs ◽  
Control Group ◽  
Vasomotor Tone ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasodilators ◽  
Pulmonary Vasodilator

We investigated the extent to which left lung autotransplantation (LLA) alters endothelium-dependent (bradykinin and acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilation in the pulmonary circulation of conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 3–4 wk post-LLA and in sham-operated controls. LLA resulted in a marked upward shift in the baseline LPQ relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The thromboxane analogue, U-46619, was used to acutely preconstrict the pulmonary circulation in control dogs, which shifted the control LPQ relationship to the same position measured post-LLA. Under these circumstances, bradykinin, acetylcholine, and nitroprusside caused pulmonary vasodilation in the control group, whereas these responses were either attenuated or reversed to vasoconstriction post-LLA. After acute preconstriction with U-46619 post-LLA, the pulmonary vasodilator responses to bradykinin and acetylcholine were again attenuated, but the response to nitroprusside was unaltered compared with control. These results indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is passively mediated and does not reflect an active increase in baseline vasomotor tone. Moreover, LLA results in an impairment in endothelium-dependent, but not endothelium-independent, pulmonary vasodilation in conscious dogs.

Responses of pulmonary and systemic circulations of perinatal goats to prostaglandin F2α

1979 ◽  
Vol 57 (2) ◽  
pp. 167-173 ◽  
Author(s):  
Charles W. Leffler ◽  
Thom L. Tyler ◽  
Sidney Cassin
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Prostaglandin F2α ◽  
Systemic Circulation ◽  
Lower Sensitivity ◽  
Adrenergic Blockade ◽  
Premature Newborn ◽  
High Doses ◽  
Pressor Agent

The effects of exogenous prostaglandin (PG) F2α, as well as PGF1α and the 15-keto metabolites of both prostaglandins, upon unventilated fetal, premature newborn, and mature newborn goat pulmonary and systemic circulations were examined by infusing the compounds into the pulmonary circulation. PGF2α is a powerful pressor agent in both pulmonary and systemic circulations of fetal and neonatal goats. Broncho–pulmonary constriction was also observed in ventilated animals at infusion rates in excess of the lung's ability to catabolize the prostaglandin. The pressor effects were not attenuated by alpha-adrenergic blockade. PGF1α is qualitatively similar, but quantitatively less, in its effect. The 15-keto metabolites did not alter pulmonary or systemic circulation even at very high doses. The PGF2α threshold dose for increasing pulmonary vascular resistance is lowest in the unventilated fetus, greatest in the premature newborn, and intermediate in the newborn older than 1 day of age. The lower sensitivity of the pulmonary circulation to the exogenous vasoconstrictor in the immediate postventilation period suggests the presence of endogenous dilator activity. Since the increase in pulmonary vascular resistance produced by indomethacin is greatest in the newly ventilated fetus, less in the older newborn, and negligible in the unventilated fetus, the substance(s) responsible for the endogenous dilator activity would appear to require prostaglandin fatty acid cyclooxygenase activity for production.

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