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.

NO and reactive oxygen species are involved in biphasic hypoxic vasoconstriction of isolated rabbit lungs

2001 ◽  
Vol 280 (4) ◽  
pp. L638-L645 ◽  
Author(s):  
Norbert Weissmann ◽  
Stefan Winterhalder ◽  
Matthias Nollen ◽  
Robert Voswinckel ◽  
Karin Quanz ◽  
...  
Keyword(s):  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Oxidase Inhibitor ◽  
No Formation ◽  
Vasoconstrictor Response ◽  
Hypoxic Vasoconstriction ◽  
Chronic Pulmonary Hypertension ◽  
Alveolar Hypoxia ◽  
Pulmonary Arterial ◽  
Synthase Inhibitor

Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion with ventilation but may also result in chronic pulmonary hypertension. It has not been clarified whether acute HPV and the response to prolonged alveolar hypoxia are triggered by identical mechanisms. We characterized the vascular response to sustained hypoxic ventilation (3% O2for 120–180 min) in isolated rabbit lungs. Hypoxia provoked a biphasic increase in pulmonary arterial pressure (PAP). Persistent PAP elevation was observed after termination of hypoxia. Total blockage of lung nitric oxide (NO) formation by N G-monomethyl-l-arginine caused a two- to threefold amplification of acute HPV, the sustained pressor response, and the loss of posthypoxic relaxation. This amplification was only moderate when NO formation was partially blocked by the inducible NO synthase inhibitor S-methylisothiourea. The superoxide scavenger nitro blue tetrazolium and the superoxide dismutase inhibitor triethylenetetramine reduced the initial vasoconstrictor response, the prolonged PAP increase, and the loss of posthypoxic vasorelaxation to a similar extent. The NAD(P)H oxidase inhibitor diphenyleneiodonium nearly fully blocked the late vascular responses to hypoxia in a dose that effected a decrease to half of the acute HPV. In conclusion, as similarly suggested for acute HPV, lung NO synthesis and the superoxide-hydrogen peroxide axis appear to be implicated in the prolonged pressor response and the posthypoxic loss of vasorelaxation in perfused rabbit lungs undergoing 2–3 h of hypoxic ventilation.

Pulmonary pressor response after prostaglandin synthesis inhibition in conscious dogs

1982 ◽  
Vol 52 (3) ◽  
pp. 705-709 ◽  
Author(s):  
B. R. Walker ◽  
N. F. Voelkel ◽  
J. T. Reeves
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Conscious Dogs ◽  
Pulmonary Pressure ◽  
Time Control ◽  
Mean Pulmonary Arterial Pressure ◽  
Before And After ◽  
Pulmonary Arterial

Recent studies have shown that vasodilator prostaglandins are continually produced by the isolated rat lung. We postulated that these vasodilators may contribute to maintenance of normal low pulmonary arterial pressure. Pulmonary pressure and cardiac output were measured in conscious dogs prior to and 30 to 60 min following administration of meclofenamate (2 mg/kg iv, followed by infusion at 2 mg . kg-1 . h-1) or the structurally dissimilar inhibitor RO–20–5720 (1 mg/kg iv, followed by infusion at 1 mg . kg-1 . h-1). The animals were also made hypoxic with inhalation of 10% O2 before and after inhibition. Time-control experiments were conducted in which only the saline vehicle was administered. Meclofenamate or RO–20–5720 caused an increase in mean pulmonary arterial pressure and total pulmonary resistance. Cardiac output and systemic pressure were unaffected. The mild hypoxic pulmonary pressor response observed was not affected by meclofenamate. Animals breathing 30% O2 to offset Denver's altitude also demonstrated increased pulmonary pressure and resistance when given meclofenamate. It is concluded that endogenous vasodilator prostaglandins may contribute to normal, low vascular tone in the pulmonary circulation.

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.

Does leukotriene C4 mediate hypoxic vasoconstriction in isolated ferret lungs?

1990 ◽  
Vol 68 (1) ◽  
pp. 253-259 ◽  
Author(s):  
C. M. Tseng ◽  
M. McGeady ◽  
T. Privett ◽  
A. Dunn ◽  
J. T. Sylvester
Keyword(s):  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Physiological Salt Solution ◽  
Leukotriene C4 ◽  
Prostaglandin F2 Alpha ◽  
Pulmonary Vasoconstriction ◽  
Vasoconstrictor Response ◽  
Hypoxic Vasoconstriction ◽  
Pulmonary Arterial

To evaluate leukotriene (LT) C4 as a mediator of hypoxic pulmonary vasoconstriction, we examined the effects of FPL55712, a putative LT antagonist, and indomethacin, a cyclooxygenase inhibitor, on vasopressor responses to LTC4 and hypoxia (inspired O2 tension = 25 Torr) in isolated ferret lungs perfused with a constant flow (50 ml.kg-1.min-1). Pulmonary arterial injections of LTC4 caused dose-related increases in pulmonary arterial pressure during perfusion with physiological salt solution containing Ficoll (4 g/dl). FPL55712 caused concentration-related inhibition of the pressor response to LTC4 (0.6 micrograms). Although 10 micrograms/ml FPL55712 inhibited the LTC4 pressor response by 61%, it did not alter the response to hypoxia. At 100 microgram/ml, FPL55712 inhibited the responses to LTC4 and hypoxia by 73 and 71%, respectively, but also attenuated the vasoconstrictor responses to prostaglandin F2 alpha (78% at 8 micrograms), phenylephrine (68% at 100 micrograms), and KCl (51% at 40 mM). At 0.5 microgram/ml, indomethacin significantly attenuated the pressor response to arachidonic acid but did not alter responses to LTC4 or hypoxia. These results suggest that in isolated ferret lungs 1) the vasoconstrictor response to LTC4 did not depend on release of cyclooxygenase products and 2) LTC4 did not mediate hypoxic vasoconstriction.

Cardiovascular and renal effects of gamma-MSH in spontaneously hypertensive and normotensive Wistar Kyoto rats

1992 ◽  
Vol 262 (1) ◽  
pp. R77-R84 ◽  
Author(s):  
X. Y. Sun ◽  
Q. P. Feng ◽  
Q. L. Gong ◽  
L. Edvinsson ◽  
T. Hedner
Keyword(s):  
Pressor Response ◽  
Urinary Sodium Excretion ◽  
Intrathecal Administration ◽  
Renal Effects ◽  
Spontaneously Hypertensive ◽  
Melanocyte Stimulating Hormone ◽  
Pithed Rats ◽  
Wistar Kyoto ◽  
Dose Dependent Increase ◽  
Dose Dependent

The objective of this study was to compare the cardiovascular and renal effects of the two gamma-melanocyte-stimulating hormone (MSH) peptide sequences in the pro-opiomelanocortin prohormone structure in conscious, anesthetized, and pithed spontaneous hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) controls. In the conscious but not in the pithed rats, intravenous injection of gamma 2- and gamma 1-MSH induced a rapid and dose-dependent increase in mean arterial pressure (MAP), and gamma 2-MSH was more potent than gamma 1-MSH. The pressor response was more pronounced and more sustained in the SHR compared with the WKY. There were dose-dependent and significant increases in heart rate (HR) after gamma 2- and gamma 1-MSH in the SHR. At intravenous infusions of low doses of gamma 2-MSH, which did not significantly influence MAP or HR, urinary sodium excretion was significantly increased in both SHR and WKY. In conscious, but not in anesthetized rats, intracerebroventricular administration of the gamma 2-MSH peptide induced sustained increases in MAP in both SHR and WKY. After intrathecal administration, there were transient pressor effects of gamma 2-MSH. We conclude that the pro-opiomelanocortin-derived gamma 2- and gamma 1-MSH peptide sequences possess potent rapid pressor actions. The pressor effects, which require an intact sympathetic nervous system, are more pronounced in the SHR strain. Moreover, gamma 2-MSH induces natriuresis when administered in nonpressor doses in WKY and SHR.

Gender differences in hypoxic vascular response of isolated sheep lungs

1983 ◽  
Vol 55 (1) ◽  
pp. 100-104 ◽  
Author(s):  
R. C. Wetzel ◽  
J. T. Sylvester
Keyword(s):  
Pressor Response ◽  
Response Relationship ◽  
Stimulus Response ◽  
Vasoconstrictor Response ◽  
Wide Range ◽  
Pulmonary Arterial ◽  
Isolated Lungs ◽  
Relationship Of ◽  
Female Sheep

We compared the steady state stimulus-response relationship of the pulmonary circulation to graded hypoxia in isolated, in situ, blood-perfused lungs of postpubertal male and female sheep and male sheep of similar age that had been castrated within 1 wk of birth. The flow-resistive properties of the pulmonary circuit were assessed by pressure-flow curves generated over a wide range of flows (0-150 ml X min-1 X kg-1 body wt-1) at six different levels of inspired oxygen tension (PIo2) between 200 and 0 Torr. The stimulus-response relationship was quantitated by determining the pulmonary arterial pressures at a flow of 50 ml X min-1 X kg-1 (Ppa50) directly from these curves. We found that this relationship was biphasic, as previously described for other species, with a peak vasoconstrictor response at a PIo2 = 30 Torr. The isolated lungs of males and castrated males achieved a greater maximal pressor response (Ppa50 = 33 +/- 3.7 and 34.5 +/- 8 Torr, respectively) than did those of females (Ppa50 = 20.2 +/- 5.6 Torr, P less than 0.01). When the pulmonary vascular bed was maximally dilated (PIo2 = 0 Torr), there were no significant differences in the Ppa50 among the groups (Ppa50 = 15.8 +/- 4.6 in males, 11 +/- 3.5 in females, and 11.5 +/- 1.9 Torr in castrated males). There were no differences between males and castrated males at any PIo2. We conclude that the hypoxic pulmonary vasomotor response was attenuated in isolated lungs of postpubertal female sheep possibly due to the effect of female hormones.

Stimulation of lipolysis in rat heart myocytes by isoproterenol

1985 ◽  
Vol 248 (2) ◽  
pp. H208-H216 ◽  
Author(s):  
A. Kryski ◽  
K. A. Kenno ◽  
D. L. Severson
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Myocardial Cells ◽  
Cyclic Monophosphate ◽  
Rat Hearts ◽  
Triacylglycerol Content ◽  
Rat Heart Myocytes ◽  
Dose Dependent Increase ◽  
Release Of Glycerol ◽  
Dose Dependent ◽  
Stimulation Of

Calcium-tolerant myocytes were isolated from rat hearts. Isoproterenol produced a dose-dependent increase in glycerol output (lipolysis) that could be blocked by propranolol. The presence of glucose in the incubation medium enhanced the release of glycerol from myocytes but had no effect on the decline in triacylglycerol content. No incorporation of radioactivity from [U-14C]glucose into glycerol could be detected. In incubations with isoproterenol, there was a stoichiometric relationship between the glycerol output and the decrease in triacylglycerol levels. The addition of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine resulted in an increase in the basal glycerol output and an enhancement of the isoproterenol-stimulated lipolytic rate. Forskolin and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate also produced a concentration-dependent stimulation of lipolysis in myocytes. Therefore, lipolysis in isolated myocytes must be regulated by adenosine 3',5'-cyclic monophosphate-dependent mechanisms. These results demonstrate that lipolysis can be observed in myocardial cells and that the lipolytic response to isoproterenol cannot be secondary to a physiological (inotropic) response since these myocyte preparations are quiescent.

Treatment with 5-HT potentiates development of pulmonary hypertension in chronically hypoxic rats

1997 ◽  
Vol 272 (3) ◽  
pp. H1173-H1181 ◽  
Author(s):  
S. Eddahibi ◽  
B. Raffestin ◽  
I. Pham ◽  
J. M. Launay ◽  
P. Aegerter ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Ventricular Hypertrophy ◽  
Potential Role ◽  
Pressor Response ◽  
Acute Hypoxia ◽  
Synthesis Inhibitor ◽  
Pulmonary Arterial ◽  
Isolated Lungs ◽  
Dose Dependent

The aim of this study was to investigate the potential role of 5-hydroxytryptamine (5-HT) on development of pulmonary hypertension during chronic exposure to mild (15% O2) and severe (10% O2) hypoxia. In isolated lungs from normoxic rats preconstricted with U-46619, 5-HT (10(-12)-10(-8) M) induced dose-dependent vasodilation (n = 6), which was suppressed by the NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME, 10(-4) M, n = 5) and reduced by the 5-HT3-receptor antagonist MDL-7222 (10(-5) M, n = 6). The vasoconstriction that was observed with higher concentrations of 5-HT (10(-7)-10(-4) M) was inhibited by ketanserin (10(-5) M) and methiothepin (10(-5) M, n = 6 each). The vasodilator response to 5-HT was suppressed in lungs from rats exposed to 10% O2 but not 15% O2 (n = 6 each). In conscious rats, intravenous administration of 5-HT potentiated the pulmonary pressor response to acute hypoxia (10% O2, n = 5), an effect that remained unchanged after pretreatment with a 5-HT1 and a 5-HT2 antagonist (n = 4) but was attenuated after treatment with the cyclooxygenase inhibitor meclofenamate (n = 4). Treatment with 5-HT (5 nmol/h i.v. by osmotic pumps) for 2 wk in rats simultaneously exposed to 10% O2 increased pulmonary arterial pressure, right ventricular hypertrophy, and muscularization of pulmonary vessels in comparison with their hypoxic controls (n = 12 each). No changes occurred in 15% O2 hypoxic rats (n = 12 each). The present findings show that 5-HT potentiates development of pulmonary hypertension in rats exposed to chronic hypoxia.

Pressor responses to central hypertonic NaCl stimulation in conscious turkeys

1986 ◽  
Vol 251 (2) ◽  
pp. R258-R263
Author(s):  
J. C. Lee ◽  
D. M. Denbow ◽  
M. D. Ashen ◽  
A. D. Roudabush
Keyword(s):  
Pressor Response ◽  
Renin Angiotensin System ◽  
Guide Cannula ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Arterial Blood ◽  
Pressor Responses ◽  
The Mean ◽  
Dose Dependent Increase ◽  
Dose Dependent

The purpose of this investigation was to examine the possible involvement of the central renin-angiotensin system in the pressor response to the intracerebroventricular (icv) injection of hypertonic NaCl in conscious turkeys. The icv injection was accomplished via a stereotaxically implanted stainless steel guide cannula in the lateral cerebral ventricle. The arterial blood pressure (AP) of the turkey was measured by means of a PE catheter in the left brachial artery. The icv administration of hypertonic NaCl caused a dose-dependent increase of AP. The mean AP increases due to 10-microliter icv injections of 0.9, 3.6, and 7.2% NaCl were 1.4 +/- 1.4, 18.1 +/- 3.0, and 31.2 +/- 3.2 (SE) mmHg, respectively. These changes were statistically significant (P less than 0.001). The icv administration of captopril, [Sar1, Ile8]angiotensin II, or pentobarbital sodium markedly reduced the pressor response to the icv injection of hypertonic 7.2% NaCl. Blockade of central adrenergic receptors with phentolamine and propranolol was without effect. These results support the contention that the central renin-angiotensin system may directly contribute to pressor responses induced by central hypertonic NaCl stimulation.

Staphylococcal alpha-toxin induced ventilation-perfusion mismatch in isolated blood-free perfused rabbit lungs

1993 ◽  
Vol 74 (4) ◽  
pp. 1972-1980 ◽  
Author(s):  
D. Walmrath ◽  
M. Scharmann ◽  
R. Konig ◽  
J. Pilch ◽  
F. Grimminger ◽  
...  
Keyword(s):  
Gas Exchange ◽  
Pressor Response ◽  
Lung Edema ◽  
Alpha Toxin ◽  
Edema Formation ◽  
Perfusate Flow ◽  
Vasoconstrictor Response ◽  
Pulmonary Arterial ◽  
Thromboxane Receptor Antagonist ◽  
A Minor

Gas exchange conditions in blood-free perfused isolated rabbit lungs were assessed by the use of the multiple inert gas elimination technique. Under baseline conditions, unimodal narrow distribution of perfusion and ventilation to midrange-ventilation-perfusion (VA/Q) areas was noted. Intravascular challenge with staphylococcal alpha-toxin caused a rapid increase in pulmonary arterial pressure (to > 40 mmHg within approximately 15 min) and delayed-onset (> 10–15 min) lung edema formation, with unaltered ventilation pressures. The vasoconstrictor response was paralleled by a progressive, severe leftward shift of perfusion to areas with low-VA/Q ratios, accompanied by a minor fraction of shunt flow. At pulmonary arterial pressures > 40 mmHg, extreme VA/Q mismatch with near absence of perfusate flow to midrange-VA/Q areas was registered. Vasoconstrictor response and VA/Q mismatch, but not the progressive edema formation, were virtually completely suppressed in lungs pretreated with acetylsalicylic acid or the thromboxane receptor antagonist BM 13505. Moreover, "rescue" application of BM 13505 after onset of alpha-toxin-induced pressor response and gas exchange abnormalities completely reversed pressure elevation and loss of VA/Q matching. We conclude that the marked vasoconstrictor response to staphylococcal alpha-toxin is paralleled by severe VA/Q mismatch with predominant perfusion of low-VA/Q areas independent of lung edema formation. Pressor response and VA/Q mismatch, but not vascular leakage, are suppressed by thromboxane inhibition.

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