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.

Effect of puberty and estradiol on hypoxic vasomotor response in isolated sheep lungs

1984 ◽  
Vol 56 (5) ◽  
pp. 1199-1203 ◽  
Author(s):  
R. C. Wetzel ◽  
H. A. Zacur ◽  
J. T. Sylvester
Keyword(s):  
Gender Difference ◽  
Acute Hypoxia ◽  
Response Relationship ◽  
Male And Female ◽  
Stimulus Response ◽  
Vasoconstrictor Response ◽  
Wide Range ◽  
Isolated Lungs ◽  
Relationship Of ◽  
Female Sheep

We previously reported that in isolated lungs from 6-mo-old sheep acute hypoxia caused a greater vasoconstrictor response in males than in females but that this response in castrated males was not different from noncastrated males. To determine whether a gender difference exists before puberty, we compared the steady-state stimulus-response relationship of the pulmonary circulation to graded hypoxia in isolated perfused lungs of juvenile 2-mo-old male and female sheep. The flow-resistive properties of the pulmonary vessels were assessed by pressure-flow curves generated over a wide range of flows (0–150 ml X min-1 X kg-1) at six different levels of inspired O2 tension (PIO2) between 200 and 0 Torr. The stimulus-response relationship, quantified by plotting the pulmonary arterial pressure at a flow of 50 ml X min-1 X kg-1 against PIO2 was the same in juvenile male and female sheep lungs. Furthermore, the responses of juvenile sheep were not different from those of 6-mo-old males and were greater than those of 6-mo-old females. Treatment with 17 beta-estradiol (10–20 mg im) 2–5 days prior to perfusion significantly attenuated the response in the lungs from both 2-mo-old female and 6-mo-old castrated male sheep. We conclude that the gender difference in the hypoxic stimulus-response relationship observed in isolated lungs from 6-mo-old sheep arises from attenuation in the female at the time of puberty. This attenuation may be mediated by estradiol.

scholarly journals Indices for Testing Neural Codes

2008 ◽  
Vol 20 (12) ◽  
pp. 2895-2936 ◽  
Author(s):  
Jonathan D. Victor ◽  
Sheila Nirenberg
Keyword(s):  
Neural Code ◽  
Response Relationship ◽  
Information Theoretic ◽  
Systems Neuroscience ◽  
Transmitted Information ◽  
Stimulus Response ◽  
Wide Range ◽  
Relationship Of ◽  
The Relationship ◽  
Rule Out

One of the most critical challenges in systems neuroscience is determining the neural code. A principled framework for addressing this can be found in information theory. With this approach, one can determine whether a proposed code can account for the stimulus-response relationship. Specifically, one can compare the transmitted information between the stimulus and the hypothesized neural code with the transmitted information between the stimulus and the behavioral response. If the former is smaller than the latter (i.e., if the code cannot account for the behavior), the code can be ruled out. The information-theoretic index most widely used in this context is Shannon's mutual information. The Shannon test, however, is not ideal for this purpose: while the codes it will rule out are truly nonviable, there will be some nonviable codes that it will fail to rule out. Here we describe a wide range of alternative indices that can be used for ruling codes out. The range includes a continuum from Shannon information to measures of the performance of a Bayesian decoder. We analyze the relationship of these indices to each other and their complementary strengths and weaknesses for addressing this problem.

Effects of indomethacin on estradiol-induced attenuation of hypoxic vasoconstriction in lamb lungs

1986 ◽  
Vol 61 (6) ◽  
pp. 2116-2121 ◽  
Author(s):  
J. B. Gordon ◽  
R. C. Wetzel ◽  
M. L. McGeady ◽  
N. F. Adkinson ◽  
J. T. Sylvester
Keyword(s):  
Steady State ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Response Relationship ◽  
Stimulus Response ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Vasodilator ◽  
Hypoxic Vasoconstriction ◽  
Pulmonary Arterial ◽  
Isolated Lungs

To determine whether cyclooxygenase products mediated the attenuation of hypoxic pulmonary vasoconstriction induced by estradiol, we measured pulmonary arterial pressure at a flow of 50 ml X min-1 X kg-1 (Ppa50) during steady-state exposures to inspired O2 tensions (PIO2) between 0 and 200 Torr in isolated lungs of juvenile ewes. Intramuscular estradiol (10 mg) 44–60 h before study significantly decreased perfusate concentrations of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of the pulmonary vasodilator, prostacyclin, but did not significantly affect the stimulus-response relationship between PIO2 and Ppa50. Estradiol (20 mg) 3–5 days before study increased 6-keto-PGF1 alpha concentrations and decreased Ppa50 at PIO2 of 10, 30, and 50 Torr. Indomethacin added to the perfusate of these lungs reduced 6-keto-PGF1 alpha to undetectable levels and altered the estradiol-induced attenuation, increasing Ppa50 at PIO2 of 10 and 30 Torr, but decreasing Ppa50 at PIO2 of 200 Torr. Despite these effects, Ppa50 remained lower than the values measured in lungs not treated with estradiol. These results suggest that the estradiol-induced attenuation of the hypoxic stimulus-response relationship was mediated only in part by cyclooxygenase products, the net effects of which were vasodilation at PIO2 of 10 and 30 Torr, but vasoconstriction at PIO2 of 200 Torr.

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.

Steady-state vascular responses to graded hypoxia in isolated lungs of five species

1981 ◽  
Vol 51 (5) ◽  
pp. 1214-1219 ◽  
Author(s):  
M. D. Peake ◽  
A. L. Harabin ◽  
N. J. Brennan ◽  
J. T. Sylvester
Keyword(s):  
Steady State ◽  
Species Differences ◽  
Response Relationship ◽  
Vasomotor Tone ◽  
Vascular Responses ◽  
Stimulus Response ◽  
Pulmonary Vasodilation ◽  
Isolated Lungs

In the isolated pig lung exposed to graded levels of hypoxia, steady-state pulmonary vasomotor tone is maximum at an O2 tension (PO2) of 50 Torr. Below 50-Torr decreases in PO2 cause steady-state tone to fall below this maximum. To determine whether this stimulus-response relation was peculiar to pigs, we measured the steady-state relation between PO2 and vasomotor tone in the isolated lungs of dogs, rabbits, cats, and ferrets, by using identical techniques in each species. Marked species differences were apparent in both the level of PO2 required to elicit responses and the amplitude of the responses. The ferret and the pig had the largest vasoconstrictor responses to hypoxia. No significant responses were obtained in the dog. The cat and rabbit were intermediate responders. In the ferret, cat, and rabbit, the stimulus-response relationship was biphasic, as in the pig. On the average, maximal constriction occurred at an PO2 of 25 Torr. When PO2 was lowered below 25 Torr, steady-state tone fell. Thus pulmonary vasodilation at low PO2 occurs in the isolated lungs of several species.

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.

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.

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.

Mechanical Properties and Reactivity of Vessels in Isolated Perfused Lungs of Chronically Hypoxic Rats

1981 ◽  
Vol 61 (5) ◽  
pp. 569-580 ◽  
Author(s):  
Celia J. Emery ◽  
Denise Bee ◽  
Gwenda R. Barer
Keyword(s):  
Vascular Tone ◽  
Chronic Hypoxia ◽  
Arterial Compliance ◽  
Ang Ii ◽  
Littermate Control ◽  
Small Vessels ◽  
Wide Range ◽  
Pulmonary Arterial ◽  
Isolated Lungs ◽  
Vasodilator Action

1. Chronically hypoxic rats kept in 10% (v/v) O2 for 3–6 weeks, were compared with littermate control rats. Pulmonary vascular resistance, measured from the slope of the pressure-flow relationship in isolated lungs perfused with blood of normal packed cell volume was higher in chronically hypoxic than control rats even during normoxia. 2. Chronically hypoxic rats weighed less than control rats but their pulmonary vascular volume, measured with labelled albumin was similar to control rats. This, together with evidence that the number of precapillary vessels is not reduced, does not suggest a large reduction in the vascular bed in chronic hypoxia. 3. A greater vasodilator action of isoprenaline and adenosine in chronically hypoxic than control lungs suggested a higher normoxic vascular tone. This higher tone was not the sole cause of increased resistance in chronically hypoxic lungs, since maximal vasodilatation did not reduce resistance to control levels. The chief cause was probably encroachment of new muscle on the vascular lumen of small vessels. 4. Pulmonary arterial compliance was reduced in chronically hypoxic lungs. 5. Reactivity of vessels to ventilation hypoxia, over a wide range of oxygen tension, to angiotensin II (ANG II) and to adenosine 5′-triphosphate (ATP) was significantly greater in chronically hypoxic than control lungs, but thresholds to these stimuli were not reduced.

Pulmonary vasoconstrictor responses to graded decreases in precapillary blood PO2 in intact-chest cat

1981 ◽  
Vol 51 (4) ◽  
pp. 1009-1016 ◽  
Author(s):  
A. L. Hyman ◽  
R. T. Higashida ◽  
E. W. Spannhake ◽  
P. J. Kadowitz
Keyword(s):  
Arterial Pressure ◽  
Pressor Response ◽  
Venous Blood ◽  
Pulmonary Veins ◽  
Right Atrial ◽  
Mixed Venous Blood ◽  
Arterial Blood ◽  
Vasoconstrictor Response ◽  
Pulmonary Arterial ◽  
Alveolar Capillary

The effects of graded changes in pulmonary lobar arterial blood PO2 and ventilatory hypoxia were investigated in the intact-chest cat under conditions of controlled lobar blood flow. A reduction in precapillary PO2 from systemic arterial levels to below 60 Torr increased lobar arterial pressure. Ventilation with 10% O2 increased lobar arterial pressure, and responses to ventilatory hypoxia and precapillary hypoxemia were independent but additive. The magnitude of the pressor response to precapillary hypoxemia was similar in experiments in which the lung was autoperfused with right atrial blood or cross-perfused with aortic blood from a donor cat breathing 10% O2. During retrograde perfusion of the ventilated lung, a reduction in pulmonary venous PO2 to 40 Torr did not affect inflow pressure. The present data suggest that sensor sites upstream to the alveolar-capillary region in segments of lobar artery unexposed to alveolar gas sense a reduction in precapillary blood PO2 and elicit a pulmonary vasoconstrictor response. The sensor site in the precapillary segment is independent of sensors in the alveolar-capillary-exposed segment region, and the effects of stimulation of both sensors on the pulmonary vascular bed are additive. In addition, the present data indicate that sensors in the pulmonary veins do not sense a reduction in PO2 in venous blood and elicit a vasoconstrictor response. These data suggest that the mixed venous blood PO2 may exert an important regulatory role in controlling pulmonary arterial pressure and pulmonary vascular resistance in the cat under normal and pathological conditions.

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