Nitric oxide decreases lung liquid production via guanosine 3′,5′-cyclic monophosphate

2001 ◽  
Vol 280 (5) ◽  
pp. L923-L929 ◽  
Author(s):  
James J. Cummings ◽  
Huamei Wang
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Epithelium ◽  
Fetal Sheep ◽  
Cgmp Analog ◽  
Pulmonary Arterial ◽  
Series Of Experiments ◽  
Lung Liquid ◽  
Tracer Dilution ◽  
Induced Changes

We studied the role of cGMP in nitric oxide (NO)-induced changes in lung liquid production ( J v ) in chronically instrumented fetal sheep. Forty-five studies were done in which J v was measured by a tracer dilution technique. Left pulmonary arterial flow (Qlpa) was measured by a Doppler flow probe. There were two series of experiments. In the first, we gave 8-bromo-cGMP, a cGMP analog, by either the pulmonary vascular or intraluminal route; in the second, we used agents to inhibit or enhance endogenous cGMP activity. When infused directly into the pulmonary circulation, 8-bromo-cGMP significantly increased Qlpa but had no effect on J v. Conversely, when instilled into the lung liquid, 8-bromo-cGMP had no effect on Qlpa but significantly reduced J v. Inhibition of guanylate cyclase activity with methylene blue totally blocked, whereas phosphodiesterase inhibition with Zaprinast significantly enhanced, the effect of instilled NO on J v. Thus the reduction in lung liquid caused by NO appears to be mediated by cGMP, perhaps through a direct effect on the pulmonary epithelium.

Nitric oxide decreases lung liquid production in fetal lambs

1997 ◽  
Vol 83 (5) ◽  
pp. 1538-1544 ◽  
Author(s):  
James J. Cummings
Keyword(s):  
Nitric Oxide ◽  
Control Period ◽  
Isotonic Saline ◽  
Fetal Lung ◽  
Similar Reduction ◽  
Pulmonary Hemodynamics ◽  
Fetal Sheep ◽  
Before And After ◽  
Pulmonary Arterial ◽  
Lung Liquid

Cummings, James J. Nitric oxide decreases lung liquid production in fetal lambs. J. Appl. Physiol. 83(5): 1538–1544, 1997.—To examine the effect of nitric oxide on fetal lung liquid production, I measured lung liquid production in fetal sheep at 130 ± 5 days gestation (range 122–137 days) before and after intrapulmonary instillation of nitric oxide. Thirty-one studies were done in which net lung luminal liquid production ( Jv) was measured by plotting the change in lung luminal liquid concentration of radiolabeled albumin, an impermeant tracer that was mixed into the lung liquid at the start of each study. To see whether changes in Jv might be associated with changes in pulmonary hemodynamics, pulmonary and systemic pressures were measured and left pulmonary arterial flow was measured by an ultrasonic Doppler flow probe. Variables were measured during a 1- to 2-h control period and for 4 h after a small bolus of isotonic saline saturated with nitric oxide gas (10 or 100%) was instilled into the lung liquid. Control (saline) instillations ( n = 6) caused no change in any variable over 6 h. Nitric oxide instillation significantly decreased Jv and increased pulmonary blood flow; these effects were sustained for 1–2 h. There was also a significant but transient decrease in pulmonary arterial pressure. Thus intrapulmonary nitric oxide causes a significant decrease in lung liquid and is associated with a decrease in pulmonary vascular resistance. In a separate series of experiments either amiloride or benzamil, which blocks Na+transport, was mixed into the lung liquid before nitric oxide instillation; still, there was a similar reduction in lung liquid production. Thus the reduction in lung liquid secretion caused by nitric oxide does not appear to depend on apical Na+ efflux.

scholarly journals The role of nitric oxide synthase in exercise induced changes in endothelial progenitor cell number

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Patrick Nicholas Colleran ◽  
Miles A. Tanner ◽  
Shena L. Latcham ◽  
Sara L. Collier ◽  
M. Harold Laughlin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Cell Number ◽  
Endothelial Progenitor ◽  
Exercise Induced ◽  
Induced Changes ◽  
Oxide Synthase

Nitric oxide decreases endothelin-1 secretion through the activation of soluble guanylate cyclase

2004 ◽  
Vol 286 (5) ◽  
pp. L984-L991 ◽  
Author(s):  
Lisa K. Kelly ◽  
Stephen Wedgwood ◽  
Robin H. Steinhorn ◽  
Stephen M. Black
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Primary Cultures ◽  
No Donor ◽  
Endothelin 1 ◽  
Cgmp Analog ◽  
Pulmonary Arterial ◽  
Long Acting ◽  
Arterial Endothelial Cells

The use of exogenous nitric oxide (NO) has been shown to alter the regulation of other endothelially derived mediators of vascular tone, such as endothelin-1 (ET-1). However, the interaction between NO and ET-1 appears to be complex and remains incompletely understood. One of the major actions of NO is the activation of soluble guanylate cyclase (sGC) with the subsequent generation of cGMP. Therefore, we undertook this study to test the hypothesis that NO regulates ET-1 production via the activation of the sGC/cGMP pathway. The results obtained indicated that the exposure of primary cultures of 4-wk-old ovine pulmonary arterial endothelial cells (4-wk PAECs) to the long-acting NO donor DETA NONOate induced both a dose- and time-dependent decrease in secreted ET-1. This decrease in ET-1 secretion occurred in the absence of changes in endothelin-converting enzyme-1 or sGC expression but in conjunction with a decrease in prepro-ET-1 mRNA. The changes in ET-1 release were inversely proportional to the cellular cGMP content. Furthermore, the NO-independent activator of sGC, YC-1, or treatment with a cGMP analog also produced significant decreases in ET-1 secretion. Conversely, pretreatment with the sGC inhibitor ODQ blocked the NO-induced decrease in ET-1. Therefore, we conclude that exposure of 4-wk PAECs to exogenous NO decreases secreted ET-1 resulting from the activation of sGC and increased cGMP generation.

Effects of elevated fetal cortisol concentrations on the volume, secretion, and reabsorption of lung liquid

1995 ◽  
Vol 269 (4) ◽  
pp. R881-R887 ◽  
Author(s):  
M. J. Wallace ◽  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Plasma Cortisol ◽  
Fetal Lung ◽  
Liquid Volume ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Age Related ◽  
Lung Liquid ◽  
Secretion Rates ◽  
Related Increase

We have examined the role of cortisol in the gestational age-related increase in the ability of epinephrine to inhibit the secretion and induce the reabsorption of fetal lung liquid. Chronically catheterized fetal sheep were infused with either saline (n = 6) or increasing doses of cortisol (1.5-3.5 mg/day; n = 6) between 120 and 130 days of gestation (term approximately 145 days). Lung liquid volumes and secretion rates were measured at 120 days (before infusion) and at 125 days, and then at 130 days we tested the ability of epinephrine to inhibit lung liquid secretion and induce liquid reabsorption. Cortisol infusions increased fetal plasma cortisol and 3,5,3'-triiodothyronine (T3) concentrations to levels observed just before labor and significantly increased the age-related increase in fetal lung liquid volume and secretion rate. At 130 days, epinephrine caused a significantly greater rate of lung liquid reabsorption in cortisol-infused fetuses (10.3 +/- 2.3 ml/h) than in saline-infused fetuses (1.5 +/- 1.6 ml/h). We conclude that a premature elevation in circulating fetal cortisol concentrations, probably in conjunction with elevated T3 concentrations, prematurely increases the epinephrine-induced reabsorption of fetal lung liquid. It is likely, therefore, that the preparturient increase of fetal cortisol concentrations plays an important role in the clearance of lung liquid at birth.

Pulmonary vasodilator drugs decrease lung liquid production in fetal sheep

1995 ◽  
Vol 79 (4) ◽  
pp. 1212-1218 ◽  
Author(s):  
J. J. Cummings
Keyword(s):  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Blood Flow ◽  
Fetal Lung ◽  
Prostaglandin D2 ◽  
Fetal Sheep ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial ◽  
Lung Liquid

To examine a potential relationship between pulmonary vasodilatation and fetal lung liquid production, I measured lung liquid production in 20 fetal sheep at 130 +/- 4 days gestation while using several agents known to increase pulmonary blood flow. Thirty-two studies were done in which left pulmonary arterial flow (Qlpa) was measured by an ultrasonic Doppler flow probe and net lung luminal liquid production (Jv) was measured by plotting the change in lung luminal liquid concentration of radiolabeled albumin, an impermeant tracer that was mixed into the lung liquid at the start of each study. Qlpa and Jv were measured during a 1- to 2-h baseline period and then during a 1- to 2-h infusion period in which the fetuses received either an intravenous infusion of acetylcholine (n = 8), prostaglandin D2 (n = 10), or the leukotriene blocker FPL-55712 (n = 7). These vasodilators work by different mechanisms, each mechanism having been implicated in the decrease in pulmonary vascular resistance seen at birth. Control (saline) infusions (n = 7) caused no change in either Qlpa or Jv over 4 h. All vasodilator agents significantly increased pulmonary blood flow and decreased Jv. Pulmonary arterial pressure did not change significantly in either the control, acetylcholine, prostaglandin, or leukotriene-blocker studies, indicating that pulmonary vascular resistance decreased. Thus agents that increase pulmonary blood flow by mechanisms that occur at birth also decrease lung liquid production in fetal lambs.

Role of airway nitric oxide on the regulation of pulmonary circulation by carbon dioxide

2001 ◽  
Vol 91 (3) ◽  
pp. 1121-1130 ◽  
Author(s):  
Yasushi Yamamoto ◽  
Hitoshi Nakano ◽  
Hiroshi Ide ◽  
Toshiyuki Ogasa ◽  
Toru Takahashi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
No Synthase ◽  
No Production ◽  
Pulmonary Vasoconstriction ◽  
Exhaled No ◽  
Progressive Hypoxia ◽  
Pulmonary Arterial

The effects of hypercapnia (CO2) confined to either the alveolar space or the intravascular perfusate on exhaled nitric oxide (NO), perfusate NO metabolites (NOx), and pulmonary arterial pressure (Ppa) were examined during normoxia and progressive 20-min hypoxia in isolated blood- and buffer-perfused rabbit lungs. In blood-perfused lungs, when alveolar CO2concentration was increased from 0 to 12%, exhaled NO decreased, whereas Ppa increased. Increments of intravascular CO2levels increased Ppa without changes in exhaled NO. In buffer-perfused lungs, alveolar CO2 increased Ppa with reductions in both exhaled NO from 93.8 to 61.7 (SE) nl/min ( P < 0.01) and perfusate NOx from 4.8 to 1.8 nmol/min ( P < 0.01). In contrast, intravascular CO2 did not affect either exhaled NO or Ppa despite a tendency for perfusate NOx to decline. Progressive hypoxia elevated Ppa by 28% from baseline with a reduction in exhaled NO during normocapnia. Alveolar hypercapnia enhanced hypoxic Ppa response up to 50% with a further decline in exhaled NO. Hypercapnia did not alter the apparent K m for O2, whereas it significantly decreased the V max from 66.7 to 55.6 nl/min. These results suggest that alveolar CO2 inhibits epithelial NO synthase activity noncompetitively and that the suppressed NO production by hypercapnia augments hypoxic pulmonary vasoconstriction, resulting in improved ventilation-perfusion matching.

scholarly journals Nitric oxide and pulmonary arterial hypertension

2017 ◽  
Vol 2017 (2) ◽  
Author(s):  
Adrian H Chester ◽  
Magdi H Yacoub ◽  
Salvador Moncada
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Tone ◽  
Pathological Changes ◽  
Pulmonary Endothelium ◽  
Physiological Conditions ◽  
Vasoactive Factors ◽  
Pulmonary Arterial

The pathogenesis of pulmonary arterial hypertension remains undefined. Changes in the expression and effects mediated by a number of vasoactive factors have been implicated to play a role in the onset and progression of the disease. The source of many of these mediators, such as nitric oxide (NO), prostacyclin and endothelin-1 (ET-1), is the pulmonary endothelium. This article focus in the role of nitric oxide in PAH, reviewing the evidence for its involvement in regulation of pulmonary a vascular tone under physiological conditions, the mechanisms by which it can contribute to the pathological changes seen in PAH and strategies for the use of NO as a therapy for treatment of the disease. 

Role of Nitric Oxide in Hypoxia-Induced Changes in Newborn Rats

Neonatology ◽  
2000 ◽  
Vol 78 (3) ◽  
pp. 191-197 ◽  
Author(s):  
İlknur Kiliç ◽  
B. Alper Kiliç ◽  
Cengiz Güven ◽  
Ediz Demirpençe ◽  
M. Arif Akşit
Keyword(s):  
Nitric Oxide ◽  
Newborn Rats ◽  
Induced Changes

scholarly journals Role of protein kinase G in nitric oxide- and cGMP-induced relaxation of newborn ovine pulmonary veins

1999 ◽  
Vol 87 (3) ◽  
pp. 993-998 ◽  
Author(s):  
Yuansheng Gao ◽  
Srinivas Dhanakoti ◽  
Jean-Francois Tolsa ◽  
J. Usha Raj
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Biochemical Study ◽  
Critical Role ◽  
Pulmonary Veins ◽  
Protein Kinase G ◽  
Fourth Generation ◽  
Cgmp Analog ◽  
A Cell

In a variety of systemic blood vessels, protein kinase G (PKG) plays a critical role in mediating relaxation induced by agents that elevate cGMP, such as nitric oxide. The role of PKG in nitric oxide- and cGMP-induced relaxation is less certain in the pulmonary circulation. In the present study, we examined the effects of inhibitors of PKG on the responses of isolated fourth-generation pulmonary veins of newborn lambs (10 ± 1 days of age) to nitric oxide and cGMP. In vessels preconstricted with endothelin-1, nitric oxide and 8-bromo-cGMP (a cell-membrane-permeable cGMP analog) induced concentration-dependent relaxation. The relaxation was significantly attenuated by β-phenyl-1, N 2-etheno-8-bromoguanosine-3′,5′-cyclic monophosphorothionate (Rp-8-Br-PET-cGMPS; a PKG inhibitor) and N-[2-(methylamino)ethyl]5-isoquinolinesulfonamide [H-8; an inhibitor of PKG and protein kinase A (PKA)] but was not affected by KT-5720 (a PKA inhibitor). Biochemical study showed that PKG activity in newborn ovine pulmonary veins was inhibited by 8-Br-PET-cGMPS and H-8 but not by KT-5720. PKA activity was not affected by 8-Br-PET-cGMPS but was inhibited by H-8 and KT-5720. These results suggest that PKG is involved in relaxation of pulmonary veins of newborn lambs induced by nitric oxide and cGMP.

Sign in / Sign up

Export Citation Format

Share Document