Effects of cyclooxygenase inhibition on pulmonary vascular responses to serotonin

1987 ◽  
Vol 62 (3) ◽  
pp. 1192-1200 ◽  
Author(s):  
W. F. Hofman ◽  
I. C. Ehrhart
Keyword(s):  
Blood Volume ◽  
Left Lung ◽  
Venous Occlusion ◽  
Cyclooxygenase Inhibitors ◽  
Cyclooxygenase Inhibition ◽  
Fourfold Increase ◽  
Lung Lobe ◽  
Before And After ◽  
Pulmonary Arterial ◽  
Dose Dependent

The vasopressor response to graded bolus doses (50–500 micrograms) of serotonin (5-hydroxytryptamine; 5-HT) was examined in the isolated canine lower left lung lobe (LLL) perfused at constant flow with autogenous blood before and after cyclooxygenase inhibition (COI). Lobar vascular resistance (LVR) was partitioned into pre- (Ra) and postcapillary (Rv) segments by venous occlusion with lobar blood volume changes monitored gravimetrically. Before COI, 5-HT produced transient, dose-dependent increases in pulmonary arterial pressure (Ppa) of 43.8 +/- 4.8–123.0 +/- 8.5% (n = 22) and simultaneous decreases in lobar blood volume (5.5 +/- 0.5–8.2 +/- 0.6 g/100 g LLL) with nearly proportionate increases in Ra and Rv at each 5-HT dose. After the initial challenge to 5-HT, LLL's were treated either with saline (n = 7) or one of three chemically distinct cyclooxygenase inhibitors. COI with 40 microM indomethacin (n = 6) or 45 microM meclofenamate (n = 6) increased resting LVR by 36.0 +/- 8.3% (P less than 0.01; n = 12) and decreased the Ra/Rv from 1.9 +/- 0.3 to 1.1 +/- 0.2 (P less than 0.01), whereas 1 mM aspirin (n = 3) caused a fourfold increase in resting LVR without affecting Ra/Rv. After indomethacin or meclofenamate treatment, the vasopressor response to graded doses of 5-HT was markedly potentiated as Ppa increased by 71.6 +/- 7.6–207.0 +/- 24.6%. COI did not potentiate the lobar vasopressor response to graded doses (10–100 micrograms) of norepinephrine (NE, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelin effects in isolated, perfused lamb lungs: role of cyclooxygenase inhibition and vasomotor tone

1991 ◽  
Vol 261 (2) ◽  
pp. H443-H450 ◽  
Author(s):  
H. Toga ◽  
J. Usha Raj ◽  
R. Hillyard ◽  
B. Ku ◽  
J. Anderson
Keyword(s):  
Vasomotor Tone ◽  
Cyclooxygenase Inhibition ◽  
Group Iii ◽  
Group I ◽  
Before And After ◽  
Pulmonary Arterial ◽  
Group Ii ◽  
Sites Of Action ◽  
Arteries And Veins

We have determined the sites of action of endothelin-1 (ET) in the lamb pulmonary circulation. The influence of cyclooxygenase inhibition and baseline vasomotor tone on ET effects was also studied. Lungs of 14 lambs (6-9 wk of age, 12.1 +/- 0.6 kg body wt) were isolated and perfused with blood. Group I lungs (n = 5) were untreated, group II lungs (n = 5) were treated with indomethacin to inhibit cyclooxygenase, and group III lungs (n = 4) were treated with indomethacin and a thromboxane A2 analogue, U-46619, to elevate vasomotor tone. All lungs were perfused with constant flow in zone 3, with left atrial and airway pressures being 8 and 6 cmH2O, respectively. We measured pulmonary arterial pressure and, by the micropuncture servo-null method, pressures in 20- to 50-microns diameter subpleural venules, both before and after each dose of ET was infused (50, 100, 250, and 500 ng/kg). Group I lungs, with high baseline vasomotor tone, exhibited a biphasic response to ET; 50-100 ng/kg of ET dilated both arteries and veins, whereas 500 ng/kg of ET constricted both arteries and veins. In group II lungs with low vasomotor tone, all doses of ET caused constriction of arteries only. In group III lungs (indomethacin treated with elevated vasomotor tone), 50-100 ng/kg of ET caused dilation of arteries and veins, whereas 500 ng/kg of ET induced constriction, this time only in arteries. We conclude that ET has both dilator and constrictor effects in arteries and veins of isolated, perfused lamb lungs. ET-induced arterial and venous dilation is dependent on initial vasomotor tone but not on cyclooxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular reactivity and permeability to serotonin in cyclooxygenase-inhibited dog lung

1988 ◽  
Vol 255 (5) ◽  
pp. H1096-H1105
Author(s):  
W. F. Hofman ◽  
I. C. Ehrhart
Keyword(s):  
Vascular Reactivity ◽  
Pressor Response ◽  
Left Lung ◽  
Base Line ◽  
Fluid Filtration ◽  
Lung Lobe ◽  
Pressor Responses ◽  
Pulmonary Arterial ◽  
Group 5 ◽  
Dose Dependent Increase

We examined the effects of serotonin (5-HT) infusion on hemodynamics, vascular compliance (Cvasc), and the filtration coefficient (Kf) in the isolated canine lower left lung lobe (LLL) perfused at constant flow. In one group (5-HT; n = 8), 5-HT was infused at 55 micrograms/min for 35 min and then at 105 micrograms/min for 15 min before and during a Kf determination. Cyclooxygenase inhibition (COI) was induced by 40 microM indomethacin (n = 4) or 45 microM meclofenamate (n = 4) before 5-HT infusion in a second group (5-HTCOI; n = 8). Control LLLs (n = 8) were given equivalent volumes of saline. The pulmonary arterial pressure (Pa) increase to 55 micrograms/min 5-HT (3.0 +/- 0.6 Torr; 43.7%) was nearly doubled (P less than 0.01) with COI (10.5 +/- 1.5 Torr; 83.3%), while LLL weight decreased 6.2 g/100 g in both groups. With 5-HT infusion, the dose-dependent increase in Pa, lobar vascular resistance, and precapillary resistance was greater (P less than 0.05) in the 5-HTCOI than the 5-HT group, but capillary pressure (Pc) was not increased from base-line values. Kf values did not differ (P greater than 0.05) among groups but Cvasc was reduced (P less than 0.05) in the 5-HTCOI group. We found that 5-HT increases Pa, but does not appear to promote microvessel fluid filtration by increasing Pc or the Kf. The enhanced and sustained pressor response to 5-HT with COI suggests that vasodilatory prostaglandins may modulate pressor responses to 5-HT.

A method for analysis of pulmonary arterial and venous occlusion data

1992 ◽  
Vol 73 (3) ◽  
pp. 1190-1195 ◽  
Author(s):  
S. H. Audi ◽  
C. A. Dawson ◽  
J. H. Linehan
Keyword(s):  
Compartmental Model ◽  
Venous Occlusion ◽  
Time Data ◽  
Equilibrium Pressure ◽  
New Approach ◽  
Lung Lobe ◽  
C Distribution ◽  
Average Slope ◽  
Arterial Inflow ◽  
Pulmonary Arterial

Recently, we presented a compartmental model of the pulmonary vascular resistance (R) and compliance (C) distribution with the configuration C1R1C2R2C3 (J. Appl. Physiol. 70: 2126–2136, 1991). This model was used to interpret the pressure vs. time data obtained after the sudden occlusion of the arterial inflow (AO), venous outflow (VO), or both inflow and outflow (DO) from an isolated dog lung lobe. In the present study, we present a new approach to the data analysis in terms of this model that is relatively simple to carry out and more robust. The data used to estimate the R′s and C′s are the steady-state arterial [Pa(0)] and venous [Pv(0)] pressures, the flow rate (Q), the area (A2) encompassed by Pa(t) after AO and the equilibrium pressure (Pd) after DO, and the average slope (m) of the Pa(t) and Pv(t) curves after VO. The following formulas can then be used to calculate the 2 R′s and 3 C′s: [Pa(0) - Pv(0)]/Q = R1 + R2 = RT, R1C1 congruent to to A2/[Pa(0) - Pd], R1 congruent to [Pa(0) - Pd]/Q, Q/m = C1 + C2 + C3 = CT, and C2 = CT - (RTC1/R2).

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.

Modulation of vascular reactivity to serotonin in the dog lung

1991 ◽  
Vol 71 (1) ◽  
pp. 217-222 ◽  
Author(s):  
W. F. Hofman ◽  
W. F. Jackson ◽  
H. el-Kashef ◽  
I. C. Ehrhart
Keyword(s):  
Arterial Pressure ◽  
Vascular Reactivity ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Venous Occlusion ◽  
Lung Lobe ◽  
Lower Lung ◽  
Pulmonary Arterial ◽  
Pressure Changes ◽  
Related Increase

Experiments were conducted to compare the effects of cyclooxygenase inhibition (COI) on vascular reactivity to serotonin (5-HT) in the isolated blood-perfused canine left lower lung lobe (LLL) and in isolated canine intrapulmonary lobar artery rings with and without a functional endothelium. LLLs (n = 6), perfused at constant blood flow, were challenged with bolus doses of 50, 100, and 250 micrograms 5-HT before COI, after COI with 45 microM meclofenamate, and after infusion of prostacyclin (PGI2) during COI. Lobar vascular resistance was segmentally partitioned by venous occlusion. Pulmonary arterial pressure increased from 13.5 +/- 1.0 to 16.3 +/- 0.8 cmH2O (P less than 0.01) after COI but declined to 13.1 +/- 1.1 cmH2O (P less than 0.01) subsequent to PGI2 infusion (91.3 +/- 14.5 ng.min-1.g LLL-1). The pulmonary arterial pressure changes were related to changes in postcapillary resistance. The dose-dependent pressor response to 5-HT was potentiated by COI (P less than 0.01) but reversibly attenuated (P less than 0.05) by PGI2 infusion. Isolated intrapulmonary artery rings (2–4 mm diam) exhibited a dose-related increase in contractile tension to 5-HT. The response to 5-HT was enhanced (P less than 0.05) in rings devoid of a functional endothelium. However, COI (10 microM indomethacin) did not alter (P greater than 0.05) the dose-related increase in contractile tension to 5-HT in rings with an intact endothelium. Our results suggest that both PGI2 and endothelium-derived relaxing factors modulate pulmonary vascular reactivity to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Species differences in pulmonary vasoactive responses to histamine, 5-hydroxytryptamine, and KCl

1993 ◽  
Vol 74 (1) ◽  
pp. 139-146 ◽  
Author(s):  
J. D. Bradley ◽  
P. B. Zanaboni ◽  
T. E. Dahms
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Species Differences ◽  
Venous Occlusion ◽  
Longitudinal Distribution ◽  
Critical Closing Pressure ◽  
Before And After ◽  
Pulmonary Arterial ◽  
Microvascular Resistance

Species differences in the longitudinal distribution of pulmonary vascular resistance (PVR) in response to 5-hydroxytryptamine (5-HT) or histamine (His) may be attributed to variations in the distribution of functional smooth muscle between arteries and veins estimated by the response to KCl. Isolated dog, guinea pig, or rabbit lungs were perfused at a constant flow = 55–75 ml.min-1.kg body wt-1. Pulmonary arterial (Ppa); arterial, double, and venous occlusion (Po,a; Pdo; Po,v, respectively); and pulmonary venous (Ppv) pressures were measured before and after increasing PVR by infusing His, 5-HT, or KCl. 5-HT and His increased Ppa--Pdo in rabbits but Pdo--Ppv in guinea pigs. In dogs, 5-HT increased Ppa--Po,a, but His increased Pdo--Ppv. Dynamic (Co,v) and static vascular compliance (CP-Q), as well as critical closing pressure (Pcc, the gamma-intercept of pressure-flow curves), were also measured. At baseline, Co,v was the same among species. However, CP-Q was higher than Co,v in all lungs and was significantly different among species in order of (in ml.cmH2O-1.100 g-1) rabbit (4.54 +/- 0.28) > guinea pig (3.31 +/- 0.18) > dog (2.21 +/- 0.13). Increases in Pcc correlated with increases in microvascular resistance (Po,a--Po,v) but not with increases in PVR after agonist infusion. KCl responses suggest that guinea pigs and rabbits have relatively more functional smooth muscle in venous and arterial microvessels, respectively, whereas dogs have approximately equal amounts.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostacyclin production with serotonin, increased flow, or elevated venous pressure in dog lung

1990 ◽  
Vol 69 (4) ◽  
pp. 1283-1289 ◽  
Author(s):  
H. A. el-Kashef ◽  
W. F. Hofman ◽  
I. C. Ehrhart
Keyword(s):  
Blood Flow ◽  
Infusion Rate ◽  
Venous Pressure ◽  
Left Lung ◽  
Blood Flow Rate ◽  
Mechanical Stimuli ◽  
Lung Lobe ◽  
Normal Blood Flow ◽  
Pulmonary Arterial ◽  
Increased Blood Flow

The lung may release prostacyclin (PGI2) in response to humoral or mechanical stimuli. We measured 6 keto-PGF1 alpha as an index of PGI2 production during serotonin (5-HT) infusion, elevated venous pressure (Pv), or increased blood flow (Q) in the isolated canine lower left lung lobe (LLL). Lobar vascular resistance (LVR) was partitioned into arterial (Ra), middle (Rm), and venous (Rv) components by arterial and venous occlusions. The infusion of 55-210 micrograms/min 5-HT (n = 9) was associated with concomitant increases in PGI2 production and dose-related increases in pulmonary arterial pressure (Pa) and LVR. 5-HT increased Ra at each infusion rate, whereas Rm was not changed and Rv was increased only at the highest infusion rate. When Pa was increased by stepwise elevations in Pv from 3.7 to 19.1 cmH2O (n = 8) or by increases in Q from 250 to 507 ml/min (n = 5) to match the Pa increase observed during 5-HT infusion, PGI2 production was not altered. Increases in Pv reduced LVR largely by decreasing Ra, whereas increases in Q reduced LVR without changing Ra, Rm, or Rv. Infusion of 5-HT when Pa was held constant by reduction in blood flow (n = 6) did not increase PGI2. Thus infusion of 5-HT at a normal blood flow rate increased PGI2 formation in the isolated blood-perfused dog lung lobe. The results also suggest that sustained mechanical effects related to increased venous pressure or elevated blood flow are not associated with a sustained elevation of PGI2 formation.

scholarly journals Continuous release of vasodilator prostanoids contributes to regulation of resting forearm blood flow in humans

1998 ◽  
Vol 274 (4) ◽  
pp. H1174-H1183 ◽  
Author(s):  
Stephen J. Duffy ◽  
Binh T. Tran ◽  
Gishel New ◽  
Ronald N. Tudball ◽  
Murray D. Esler ◽  
...  
Keyword(s):  
Blood Flow ◽  
Forearm Blood Flow ◽  
Venous Occlusion ◽  
Continuous Release ◽  
Before And After ◽  
Prostaglandin F ◽  
Resting Tone ◽  
Dose Dependent ◽  
Prostacyclin Production

Continuous release of nitric oxide contributes to the maintenance of resting tone in the human forearm and coronary circulations; however, evidence for a similar role of vasodilator prostanoids such as prostacyclin is lacking. We examined whether continuous release of prostacyclin contributes to basal forearm blood flow. Flow was measured using venous occlusion plethysmography in 38 healthy volunteers [mean age 21.3 ± 2.5 yr (±SD); 13 female, 25 male] at rest, after administration of three incremental intra-arterial infusions of either the cyclooxygenase inhibitor aspirin or placebo, and before and after administration of the endothelium-dependent and -independent dilators acetylcholine (30 μg/min) and nitroprusside (1 μg/min). To assess the effect of aspirin on the production of prostacyclin, plasma 6-keto prostaglandin F1α(6-keto-PGF1α; the stable metabolite of prostacyclin) was measured by simultaneous arterial and venous sampling. Aspirin produced a time- and dose-dependent reduction in forearm blood flow, resulting in a 32% decrease at the highest dose. The effect was maximal after 10 min. Flow at rest and after aspirin doses of 1, 3, and 10 mg/min was 2.6 ± 0.2, 2.3 ± 0.2, 2.1 ± 0.2, and 1.8 ± 0.2 ml ⋅ 100 ml forearm tissue−1 ⋅ min−1, respectively (means ± SE, P< 0.001). Commensurate with these data, the net forearm production of 6-keto-PGF1α was 52.9 ± 16.4, 11.7 ± 8.6, 18.7 ± 8.5, and 12.0 ± 12.5 pg ⋅ 100 ml forearm tissue−1 ⋅ min−1 for the respective doses ( P = 0.04). No time-dependent reduction in flow was seen in subjects with vehicle infusion. Aspirin did not affect the responses to acetylcholine or nitroprusside. These data suggest that continuous release of prostacyclin plays a role in the maintenance of resting forearm blood flow. There appears to be a direct link between the reduction in flow with aspirin and inhibition of prostacyclin production.

Pulmonary and systemic vascular responses of perinatal goats to prostaglandins E1 and E2

1979 ◽  
Vol 236 (6) ◽  
pp. H828-H832 ◽  
Author(s):  
S. Cassin ◽  
T. Tyler ◽  
C. Leffler ◽  
R. Wallis
Keyword(s):  
Dose Response ◽  
Pulmonary Circulation ◽  
Left Lung ◽  
Systemic Arterial Pressure ◽  
Lung Lobe ◽  
Response Characteristics ◽  
Arterial Blood ◽  
Pulmonary Arterial ◽  
Vasodilator Action

Effects of prostaglandins of the E series and their metabolites on pulmonary and systemic circulations of newborn and exteriorized fetal goats (anesthetized with chloralose) were evaluated in situ using an isolated perfused left lung lobe preparation. Prostaglandin E1 (PGE1) and, to a lesser extent, prostaglandin E2 (PGE2) infusions resulted in decreases of pulmonary vascular resistance (PVR) of fetal and neonatal goats. Infusions of PGE1 or PGE2 (less than 2 microgram.kg-1.min-1 for 1 min) directly into left pulmonary arterial blood did not affect systemic arterial pressure (SAP). Infusions of PGEs (greater than 2 microgram.kg-1.min-1 for 1 min) resulted in decreases in SAP and heart rate. The dose-response characteristics of the pulmonary circulation in response to PGE1 and PGE2 were not different in fetal and newborn goats. Fetal asphyxia did not alter the dose-response characteristics of pulmonary circulation in response to PGE1. Metabolites (15-keto) of PGE1 and PGE2 had no effect upon PVR or SAP of perinatal goats. These results demonstrate in perinatal mammals 1) vasodilator action of PGE1 and PGE2 on the pulmonary and systemic circulations, and 2) catabolism by the lungs of these prostaglandins.

Prostanoid inhibition potentiates vasoconstrictor response to acetylcholine in dog lung

1986 ◽  
Vol 61 (3) ◽  
pp. 1035-1040 ◽  
Author(s):  
J. D. Catravas ◽  
W. F. Hofman ◽  
I. C. Ehrhart
Keyword(s):  
Pressor Response ◽  
Phosphodiesterase Inhibitor ◽  
Left Lobe ◽  
Vasoconstrictor Response ◽  
Lower Left Lobe ◽  
Before And After ◽  
Muscarinic Cholinoceptors ◽  
Pulmonary Arterial ◽  
Dose Dependent Increase ◽  
Dose Dependent

We determined whether cyclooxygenase or phosphodiesterase inhibition would alter the vasomotor response to acetylcholine in the dog lung. Lower left lobes were removed and then cannulated, ventilated, and pump perfused with autogenous blood at constant flow [6.0 +/- 0.1 ml X min-1 X g-1 lower left lobe (LLL)]. LLLs were challenged with graded doses of acetylcholine (ACh) (100–1,000 nmol) into the arterial cannula before and after administration of either 40 microM indomethacin (n = 5), 1 mM aspirin (n = 4), or 1 mM theophylline (n = 5). ACh produced a dose-dependent increase in pulmonary arterial pressure (Pa) and a decrease in the upstream-to-down-stream resistance ratio (Rus/Rds). Pretreatment with either indomethacin or aspirin potentiated the Pa response to ACh while eliminating the ACh-associated decrease in Rus/Rds. Pretreatment with the phosphodiesterase inhibitor theophylline significantly antagonized the ACh pressor response and decrease in the Rus/Rds. The present study suggests that the pulmonary pressor response to ACh is enhanced with cyclooxygenase inhibition. Our results indicate that ACh stimulates pulmonary vascular muscarinic cholinoceptors to cause vasoconstriction. Additionally or as sequelae to this response, predominantly vasodilatory prostanoids appear to be released.

Sign in / Sign up

Export Citation Format

Share Document