scholarly journals Progressive dysfunction of nitric oxide synthase in a lamb model of chronically increased pulmonary blood flow: a role for oxidative stress

2008 ◽  
Vol 295 (5) ◽  
pp. L756-L766 ◽  
Author(s):  
Peter E. Oishi ◽  
Dean A. Wiseman ◽  
Shruti Sharma ◽  
Sanjiv Kumar ◽  
Yali Hou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Lung Tissue ◽  
Pulmonary Blood Flow ◽  
Artery Pressure ◽  
Oxide Synthase ◽  
Inhaled No

Cardiac defects associated with increased pulmonary blood flow result in pulmonary vascular dysfunction that may relate to a decrease in bioavailable nitric oxide (NO). An 8-mm graft (shunt) was placed between the aorta and pulmonary artery in 30 late gestation fetal lambs; 27 fetal lambs underwent a sham procedure. Hemodynamic responses to ACh (1 μg/kg) and inhaled NO (40 ppm) were assessed at 2, 4, and 8 wk of age. Lung tissue nitric oxide synthase (NOS) activity, endothelial NOS (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), and heat shock protein 90 (HSP90), lung tissue and plasma nitrate and nitrite (NOx), and lung tissue superoxide anion and nitrated eNOS levels were determined. In shunted lambs, ACh decreased pulmonary artery pressure at 2 wk ( P < 0.05) but not at 4 and 8 wk. Inhaled NO decreased pulmonary artery pressure at each age ( P < 0.05). In control lambs, ACh and inhaled NO decreased pulmonary artery pressure at each age ( P < 0.05). Total NOS activity did not change from 2 to 8 wk in control lambs but increased in shunted lambs (ANOVA, P < 0.05). Conversely, NOxlevels relative to NOS activity were lower in shunted lambs than controls at 4 and 8 wk ( P < 0.05). eNOS protein levels were greater in shunted lambs than controls at 4 wk of age ( P < 0.05). Superoxide levels increased from 2 to 8 wk in control and shunted lambs (ANOVA, P < 0.05) and were greater in shunted lambs than controls at all ages ( P < 0.05). Nitrated eNOS levels were greater in shunted lambs than controls at each age ( P < 0.05). We conclude that increased pulmonary blood flow results in progressive impairment of basal and agonist-induced NOS function, in part secondary to oxidative stress that decreases bioavailable NO.

Physiological alterations in increased pulmonary blood flow with and without pulmonary hypertension

1961 ◽  
Vol 16 (2) ◽  
pp. 305-308 ◽  
Author(s):  
Lois T. Ellison ◽  
David P. Hall ◽  
Thomas Yeh ◽  
H. Mobarhan ◽  
Joseph Rossi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Function ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Blood Flow ◽  
Pulmonary Artery Hypertension ◽  
Systolic Pulmonary Artery Pressure ◽  
Venous Admixture ◽  
Artery Pressure ◽  
Physiological Alterations

Alterations in pulmonary function and in hemodynamics were studied in dogs with high pulmonary blood flow resulting from systemic pulmonary artery shunts. In order to facilitate elevation in pulmonary artery pressure, the vascular bed was reduced in some cases by obstructing branches of the pulmonary artery with Teflon clips or by lobectomy. Results in 30 control dogs and in 30 animals that survived 5–36 months (average 16) following creation of shunts indicated that pulmonary function was not significantly altered by increased pulmonary blood flow until pulmonary artery hypertension developed. When systolic pulmonary artery pressure exceeded 40 mm Hg, there was a decrease in arterial Po2, an increase in venous admixture percentage of cardiac output, and an increase in the A-a O2 difference during three levels of O2 breathing, indicating both abnormal venous admixture and abnormal diffusion. Possible explanations for these findings are presented. Evidence in one dog suggests that these alterations are reversible. Submitted on August 10, 1960

Pressure-Flow Relationships in the Dog Lung During Acute, Subtotal Pulmonary Vascular Occlusion

1958 ◽  
Vol 192 (3) ◽  
pp. 613-619 ◽  
Author(s):  
Michael T. Lategola
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Blood Flow ◽  
Vascular Occlusion ◽  
Percentage Change ◽  
Artery Pressure ◽  
Vascular Bed ◽  
Change In Mean ◽  
Pulmonary Vascular Bed

The relationship of pulmonary artery pressure to pulmonary blood flow was studied in the dog by means of occlusive shifting of blood flow within the pulmonary vascular bed. All experiments were performed using the closed-chest preparation. The range of blood flow increases studied was 25–388%. A graphical plot of the percentage change in blood flow versus the percentage change in mean pulmonary artery pressure is presented. A visually estimated curve of this latter data is presented, discussed and compared to four other curves from previous pulmonary vascular studies. A comparison of these curves suggests that the relative maximum capacity of the pulmonary vascular bed of man and dog are similar. These curves plus certain assumptions allow the speculative delineation of a graphical area representing the ‘active’ vasomotor component of exercise at different levels of pulmonary blood flow increase.

Acute effects of partial compression of ductus arteriosus on fetal pulmonary circulation

1989 ◽  
Vol 257 (2) ◽  
pp. H626-H634 ◽  
Author(s):  
S. H. Abman ◽  
F. J. Accurso
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Circulation ◽  
Pulmonary Blood Flow ◽  
Ductus Arteriosus ◽  
Base Line ◽  
Acute Effects ◽  
Artery Pressure

To determine the acute effects of increased pulmonary artery pressure and flow on the fetal pulmonary circulation, we studied the response of pulmonary blood flow and vascular reactivity to partial compression of the ductus arteriosus in 22 chronically prepared late-gestation fetal lambs. An inflatable occluder was placed loosely around the ductus arteriosus for compression. Partial compression of the ductus rapidly increased mean pulmonary artery pressure from 45 +/- 1 to 60 +/- 1 mmHg (mean +/- SE) and left pulmonary artery blood flow from 65 +/- 6 to 151 +/- 11 ml/min at 30 min (P less than 0.001; 12 animals). Despite keeping pulmonary artery pressure constant, pulmonary blood flow steadily declined and by 2 h was not different from base-line values. Pulmonary vascular resistance initially fell during the first 30 min of partial compression but then steadily increased and remained elevated above base-line values for at least 30 min after the release of the occluder (P less than 0.001). The decline of pulmonary vascular resistance during the first 30 min of compression was blunted after treatment with the cyclooxygenase inhibitor, meclofenamate (P less than 0.001; 6 animals). Rapid incremental ductus compressions demonstrated a decrease in the slope of the pressure-flow relationship from 3.30 +/- 0.27 (control) to 1.59 +/- 0.21 ml.min-1.mmHg-1 during the postcompression period (P less than 0.001; 12 animals). The vasodilation response to small increases of fetal PO2 was markedly blunted during the postcompression period (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The Use of Histamine Questioned

PEDIATRICS ◽  
1976 ◽  
Vol 58 (5) ◽  
pp. 776-777
Author(s):  
Shyamal K. Sanyal
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Pulmonary Artery Pressure ◽  
Vascular Resistance ◽  
Cardiac Catheterization ◽  
Pulmonary Blood Flow ◽  
Pathogenetic Mechanism ◽  
Artery Pressure

The pathogenetic mechanism proposed by Levin et al.1 to explain the persistence of fetal cardiopulmonary circulatory pathway (PFCCP) during infancy if of interest. However, their suggestion that use of histamine injected directly into the pulmonary artery may be beneficial in such patients raises some questions. The initial cardiac catheterization data in their patient at the age of 33 days show hypoxia and hypercarbia. The authors have indicated in Table II that both of these factors could produce a decrease in pulmonary blood flow as well as an increase in pulmonary artery pressure and pulmonary vascular resistance.

VENTILATION-PERFUSION RELATIONSHIPS IN CHILDREN WITH HEART DISEASE AND DIMINISHED PULMONARY BLOOD FLOW

PEDIATRICS ◽  
1968 ◽  
Vol 42 (5) ◽  
pp. 778-785
Author(s):  
Martin H. Lees ◽  
Richard H. Burnell ◽  
Clarence L. Morgan ◽  
Benjamin B. Ross
Keyword(s):  
Blood Flow ◽  
Heart Disease ◽  
Pulmonary Artery ◽  
Pulmonary Function ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Blood Flow ◽  
Alveolar Ventilation ◽  
Uneven Distribution ◽  
Artery Pressure ◽  
Major Abnormality

Pulmonary function of infants and children with diminished pulmonary blood flow was studied by measurement of alveolar ventilation and alveolar-arterial gas tension differences of O2, CO2, and N2. The increased ventilation of these subjects was found to be effective in CO2 elimination (arterial CO2 tension, 31 mm Hg), but there was evidence of considerable unevenness of distribution of ventilation/perfusion ratios (VAQ). A measure of the degree of VA/Q unevenness was obtained by use of the urine-alveolar nitrogen tension difference. It is likely, under the prevailing conditions of hyperventilation and hypoperfusion, that maldistribution of perfusion is the major abnormality. Uneven distribution of perfusion is most probably due to the effects of gravity enhanced by low pulmonary artery pressure and blood flow—an exaggenation of the normal physiologic relative overperfusion of the lower-most parts of the lung.

Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide

2002 ◽  
Vol 92 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Daniel Nyhan ◽  
Soonyul Kim ◽  
Stacey Dunbar ◽  
Dechun Li ◽  
Artin Shoukas ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Pulmonary Artery ◽  
Lung Tissue ◽  
Rat Model ◽  
Orthostatic Intolerance ◽  
Volume Distribution ◽  
Contractile Responses ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Vascular contractile hyporesponsiveness is an important mechanism underlying orthostatic intolerance after microgravity. Baroreceptor reflexes can modulate both pulmonary resistance and capacitance function and thus cardiac output. We hypothesized, therefore, that pulmonary vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model of microgravity. Pulmonary artery (PA) contractile responses to phenylephrine (PE) and U-46619 (U4) were significantly decreased in the PAs from HLU vs. control (C) animals. N G-nitro-l-arginine methyl ester (10−5 M) enhanced the contractile responses in the PA rings from both C and HLU animals and completely abolished the differential responses to PE and U4 in HLU vs. C animals. Vasorelaxant responses to ACh were significantly enhanced in PA rings from HLU rats compared with C. Moreover, vasorelaxant responses to sodium nitroprusside were also significantly enhanced. Endothelial nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression were significantly enhanced in PA and lung tissue from HLU rats. In marked contrast, the expression of inducible nitric oxide synthase was unchanged in lung tissue. These data support the hypothesis that vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.

Sign in / Sign up

Export Citation Format

Share Document