Modulating the Pulmonary Circulation: Nitric Oxide and Beyond

2022 ◽  
pp. 105-114
Author(s):  
Thomas Schilling ◽  
Astrid Bergmann
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Circulation

Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension

1998 ◽  
Vol 84 (2) ◽  
pp. 435-441 ◽  
Author(s):  
Christophe Adrie ◽  
Fumito Ichinose ◽  
Alexandra Holzmann ◽  
Larry Keefer ◽  
William E. Hurford ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Half Life ◽  
Hemodynamic Effects ◽  
Pulmonary Vasodilation ◽  
Short Half Life ◽  
Acute Pulmonary Hypertension ◽  
Inhaled No

Adrie, Christophe, Fumito Ichinose, Alexandra Holzmann, Larry Keefer, William E. Hurford, and Warren M. Zapol. Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension. J. Appl. Physiol. 84(2): 435–441, 1998.—Sodium 1-( N, N-diethylamino)diazen-1-ium-1,2-diolate {DEA/NO; Et2N[N(O)NO]Na} is a compound that spontaneously generates nitric oxide (NO). Because of its short half-life (2.1 min), we hypothesized that inhaling DEA/NO aerosol would selectively dilate the pulmonary circulation without decreasing systemic arterial pressure. We compared the pulmonary selectivity of this new NO donor with two other reference drugs: inhaled NO and inhaled sodium nitroprusside (SNP). In seven awake sheep with pulmonary hypertension induced by the infusion of U-46619, we compared the hemodynamic effects of DEA/NO with those of incremental doses of inhaled NO gas. In seven additional awake sheep, we examined the hemodynamic effects of incremental doses of inhaled nitroprusside (i.e., SNP). Inhaled NO gas selectively dilated the pulmonary vasculature. Inhaled DEA/NO produced nonselective vasodilation; both systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were reduced. Inhaled SNP selectively dilated the pulmonary circulation at low concentrations (≤10−2 M), inducing a decrease of PVR of up to 42% without any significant decrease of SVR (−5%), but nonselectively dilated the systemic circulation at larger doses (>10−2 M). In conclusion, despite its short half-life, DEA/NO is not a selective pulmonary vasodilator compared with inhaled NO. Inhaled SNP appears to be selective to the pulmonary circulation at low doses but not at higher levels.

Endogenous nitric oxide and pulmonary circulation response to hypoxia in high-altitude adapted Tibetan sheep

2004 ◽  
Vol 93 (1-2) ◽  
pp. 190-195 ◽  
Author(s):  
Zonghai Ruan ◽  
Tomonobu Koizumi ◽  
Akio Sakai ◽  
Takeshi Ishizaki ◽  
Zhangang Wang
Keyword(s):  
Nitric Oxide ◽  
High Altitude ◽  
Pulmonary Circulation ◽  
Tibetan Sheep ◽  
Endogenous Nitric Oxide

Divergent contractile and structural responses of the murine PKC-ε null pulmonary circulation to chronic hypoxia

2005 ◽  
Vol 289 (6) ◽  
pp. L1083-L1093 ◽  
Author(s):  
C. M. Littler ◽  
C. A. Wehling ◽  
M. J. Wick ◽  
K. A. Fagan ◽  
C. D. Cool ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Circulation ◽  
Vascular Remodeling ◽  
Vascular Tone ◽  
Chronic Hypoxia ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Systolic Pressure ◽  
Structural Response ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Remodeling

Loss of PKC-ε limits the magnitude of acute hypoxic pulmonary vasoconstriction (HPV) in the mouse. Therefore, we hypothesized that loss of PKC-ε would decrease the contractile and/or structural response of the murine pulmonary circulation to chronic hypoxia (Hx). However, the pattern of lung vascular responses to chronic Hx may or may not be predicted by the acute HPV response. Adult PKC-ε wild-type (PKC-ε+/+), heterozygous null, and homozygous null (PKC-ε−/−) mice were exposed to normoxia or Hx for 5 wk. PKC-ε−/− mice actually had a greater increase in right ventricular (RV) systolic pressure, RV mass, and hematocrit in response to chronic Hx than PKC-ε+/+ mice. In contrast to the augmented PA pressure and RV hypertrophy, pulmonary vascular remodeling was increased less than expected (i.e., equal to PKC-ε+/+ mice) in both the proximal and distal PKC-ε−/− pulmonary vasculature. The contribution of increased vascular tone to this pulmonary hypertension (PHTN) was assessed by measuring the acute vasodilator response to nitric oxide (NO). Acute inhalation of NO reversed the increased PA pressure in hypoxic PKC-ε−/− mice, implying that the exaggerated PHTN may be due to a relative deficiency in nitric oxide synthase (NOS). Despite the higher PA pressure, chronic Hx stimulated less of an increase in lung endothelial (e) and inducible (i) NOS expression in PKC-ε−/− than PKC-ε+/+ mice. In contrast, expression of nNOS in PKC-ε+/+ mice decreased in response to chronic Hx, while lung levels in PKC-ε−/− mice remained unchanged. In summary, loss of PKC-ε results in increased vascular tone, but not pulmonary vascular remodeling in response to chronic Hx. Blunting of Hx-induced eNOS and iNOS expression may contribute to the increased vascular tone. PKC-ε appears to be an important signaling intermediate in the hypoxic regulation of each NOS isoform.

scholarly journals Interacting roles of nitric oxide and ATP in the pulmonary circulation of the rat

1995 ◽  
Vol 114 (4) ◽  
pp. 846-850 ◽  
Author(s):  
Haroutioun Hasséssian ◽  
Geoffrey Burnstock
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Circulation

Differential effects of nitric oxide synthase modulation on porcine systemic and pulmonary circulation in vivo

1997 ◽  
Vol 25 (2) ◽  
pp. 280-285 ◽  
Author(s):  
Peter Dahm ◽  
Johan Thorne ◽  
Evita Zoucas ◽  
Lena Martensson ◽  
Erling Myhre ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Pulmonary Circulation ◽  
Differential Effects ◽  
Oxide Synthase

scholarly journals Extracellular ATP signaling in the rabbit lung: erythrocytes as determinants of vascular resistance

2003 ◽  
Vol 285 (2) ◽  
pp. H693-H700 ◽  
Author(s):  
Randy S. Sprague ◽  
Jeffrey J. Olearczyk ◽  
Dana M. Spence ◽  
Alan H. Stephenson ◽  
Robert W. Sprung ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Vascular Resistance ◽  
Flow Rate ◽  
Vascular Endothelium ◽  
Pulmonary Circulation ◽  
Blood Cells ◽  
Atp Release ◽  
Rabbit Lung ◽  
Atp Signaling

Previously, it was reported that red blood cells (RBCs) are required to demonstrate participation of nitric oxide (NO) in the regulation of rabbit pulmonary vascular resistance (PVR). RBCs do not synthesize NO; hence, we postulated that ATP, present in millimolar amounts in RBCs, was the mediator, which evoked NO synthesis in the vascular endothelium. First, we found that deformation of RBCs, as occurs on passage across the pulmonary circulation with increasing flow rate, evoked increments in ATP release. Here, ATP (300 nM), administered to isolated, salt solution-perfused (PSS) rabbit lungs, decreased total and upstream (arterial) PVR, a response inhibited by NG-nitro-l-arginine methyl ester (l-NAME, 100 μM). In lungs perfused with PSS containing RBCs, l-NAME increased total and upstream PVR. In lungs perfused with PSS containing glibenclamide-treated RBCs, which inhibits ATP release, l-NAME was without effect. Apyrase grade VII (8 U/ml), which degrades ATP to AMP, was without effect on PVR in PSS-perfused lungs. These results are consistent with the hypothesis that ATP, released from RBCs as they traverse the pulmonary circulation, evokes endogenous NO synthesis.

Heat shock protein 90 modulates endothelial nitric oxide synthase activity and vascular reactivity in the newborn piglet pulmonary circulation

2007 ◽  
Vol 292 (6) ◽  
pp. L1515-L1525 ◽  
Author(s):  
Judy L. Aschner ◽  
Susan L. Foster ◽  
Mark Kaplowitz ◽  
Yongmei Zhang ◽  
Heng Zeng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Nitric Oxide Synthase ◽  
Heat Shock Protein ◽  
Pulmonary Circulation ◽  
Endothelial Nitric Oxide Synthase ◽  
Vascular Reactivity ◽  
Heat Shock Protein 90 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Heat shock protein 90 (Hsp90) binding to endothelial nitric oxide synthase (eNOS) is an important step in eNOS activation. The conformational state of bound Hsp90 determines whether eNOS produces nitric oxide (NO) or superoxide (O2•−). We determined the effects of the Hsp90 antagonists geldanamycin (GA) and radicicol (RA) on basal and ACh-stimulated changes in vessel diameter, cGMP production, and Hsp90:eNOS coimmunoprecipitation in piglet resistance level pulmonary arteries (PRA). In perfused piglet lungs, we evaluated the effects of GA and RA on ACh-stimulated changes in pulmonary arterial pressure (Ppa) and perfusate accumulation of stable NO metabolites (NOx−). The effects of GA and RA on ACh-stimulated O2•− generation was investigated in cultured pulmonary microvascular endothelial cells (PMVEC) by dihydroethidine (DHE) oxidation and confocal microscopy. Hsp90 inhibition with GA or RA reduced ACh-mediated dilation, abolished the ACh-stimulated increase in cGMP, and reduced eNOS:Hsp90 coprecipitation. GA and RA also inhibited the ACh-mediated changes in Ppa and NOx− accumulation rates in perfused lungs. ACh increased the rate of DHE oxidation in PMVEC pretreated with GA and RA but not in untreated cells. The cell-permeable superoxide dismutase mimetic M40401 reversed GA-mediated inhibition of ACh-induced dilation in PRA. We conclude that Hsp90 is a modulator of eNOS activity and vascular reactivity in the newborn piglet pulmonary circulation. Uncoupling of eNOS with GA or RA inhibits ACh-mediated dilation by a mechanism that involves O2•− generation.

Type I nitric oxide synthase is decreased in the fetal pulmonary circulation of hypertensive lambs

2002 ◽  
Vol 33 (6) ◽  
pp. 437-442 ◽  
Author(s):  
Ching Tzao ◽  
Peter A. Nickerson ◽  
Robin H. Steinhorn ◽  
Bernice K. Noble ◽  
Daniel D. Swartz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Pulmonary Circulation ◽  
Type I ◽  
Oxide Synthase
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