Time course of blood volume changes in an isolated lung lobe after venous pressure elevation.
*Blood Volume/drug effects; *Pulmonary Circulation; *Venous Pressure; Animals; Dogs; Extravascular Lung Water/metabolism; Female; In Vitro Techniques; Indicator Dilution Techniques; Indocyanine Green; Lung/*physiology; Male; Papaverine/pharmacology; Perfusion; Time Factors
The elevation of venous pressure (Pv) in isolated perfused organs causes organ weight to increase in a biphasic manner. The initial rapid phase results primarily from an increase in blood volume (BV), whereas the second slower phase is generally considered to reflect fluid filtration. Recent studies have suggested, however, that BV may continue to increase during the slow weight gain phase. To address this question, we made serial measurements of circulating BV by indicator dilution with indocyanine green dye in a canine isolated perfused left lower lung lobe (LLL) preparation during 40 min of Pv elevation. Pv was raised to approximately 18 Torr in six LLLs beginning an average of 28 min after the start of perfusion. After an initial rapid increase, BV continued to increase at a slower rate for approximately 30 min. The increase in BV observed between 3 and 40 min of Pv elevation [4.3 +/- 0.3 (SE) ml] was 47.9 +/- 9.1% of the weight gain that occurred during this period. In six additional LLLs, Pv elevation was delayed until approximately 70 min after the perfusion was started. In these LLLs, BV generally achieved constancy 3 min after Pv was elevated. These data indicate that the dynamics of the BV response of this preparation to Pv elevation is time dependent and that gravimetric determinations of the rate of fluid filtration may substantially overestimate the true filtration rate in the presence of continuing increases in BV. The increases in BV observed in the first group of LLLs appear to be due to vascular recruitment rather than stress relaxation.
Maron M B; Lane S M
Journal of applied physiology (Bethesda, Md. : 1985)
1994
1994-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jappl.1994.77.6.2720" target="_blank" rel="noreferrer noopener">10.1152/jappl.1994.77.6.2720</a>
Postreceptor defects in alveolar epithelial beta-adrenergic signaling after prolonged isoproterenol infusion.
8-Bromo Cyclic Adenosine Monophosphate/pharmacology; Adenylyl Cyclases/metabolism; Adrenergic; Adrenergic beta-Agonists/*pharmacology; Animals; beta/*metabolism; Colforsin/pharmacology; Cyclic AMP-Dependent Protein Kinase Type II; Cyclic AMP-Dependent Protein Kinases/metabolism; Cyclic AMP/metabolism; Extravascular Lung Water/metabolism; Isoproterenol/*pharmacology; Male; Pulmonary Alveoli/*drug effects/*metabolism; Pulmonary Edema/metabolism; Rats; Receptors; Respiratory Mucosa/drug effects/metabolism; Signal Transduction/drug effects; Sprague-Dawley
We previously found that prolonged isoproterenol (Iso) infusion in rats impaired the ability of beta-adrenoceptor (beta-AR) agonists to increase alveolar liquid clearance (ALC). Here, we determined if postreceptor defects in beta-AR signaling contribute to this impairment. Iso was infused using subcutaneous miniosmotic pumps (4, 40, or 400 microg. kg-1. h-1) in rats for 48 h. At this time, forskolin-stimulated ALC was measured by mass balance. Forskolin-stimulated ALC [33.4 +/- 2.1%/h (mean +/- SE) in vehicle-infused rats] was reduced by 25 and 38%, respectively, after the 40 and 400 microg. kg-1. h-1 Iso infusions. The ability of forskolin to increase cAMP was reduced by 70% in alveolar type II (ATII) cells isolated from rats infused with 400 microg. kg-1. h-1 Iso. Additionally, the ability of the stable cAMP analog 8-bromoadenosine-3',5'-cyclic monophosphorothioate, Sp-isomer, to increase ALC (48.7 +/- 3.0% in vehicle-infused rats) was reduced by 25 and 51%, respectively, after the 40 and 400 microg. kg-1. h-1 infusions. Finally, the ability of cAMP to increase protein kinase A activity was eliminated in ATII cells isolated from rats infused with Iso at 400 microg. kg-1. h-1. These data demonstrate that prolonged beta-AR agonist exposure can impair alveolar epithelial beta-AR signaling downstream of the beta-AR.
Morgan Eric E; Stader Sonya M; Hodnichak Cheryl M; Mavrich Kate E; Folkesson Hans G; Maron Michael B
American journal of physiology. Lung cellular and molecular physiology
2003
2003-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajplung.00339.2002" target="_blank" rel="noreferrer noopener">10.1152/ajplung.00339.2002</a>
Involvement of {alpha}ENaC and Nedd4-2 in the conversion from lung fluid secretion to fluid absorption at birth in the rat as assayed by RNA interference analysis.
*RNA Interference; Absorption; Animals; Body Fluids/*metabolism; Death; Endosomal Sorting Complexes Required for Transport; Epithelial Sodium Channels/genetics/*physiology; Extravascular Lung Water/metabolism; Gene Silencing; Lung/*metabolism; Nedd4 Ubiquitin Protein Ligases; Newborn/*metabolism; Rats; RNA; Small Interfering/metabolism; Sodium-Potassium-Exchanging ATPase/metabolism; Sprague-Dawley; Tissue Distribution; Ubiquitin-Protein Ligases/genetics/metabolism/*physiology
To explore interactions between the epithelial Na channel (ENaC) and neural precursor expressed, developmentally downregulated protein 4-2 (Nedd4-2) at the conversion of the rat lung from fluid secretion to absorption at birth, we used small-interfering RNA (siRNA) against alphaENaC and Nedd4-2. siRNA-generating plasmid DNA (pDNA) was administered via trans-thoracic intrapulmonary (ttip) injection 24 h before ENaC and Nedd4-2 expression, extravascular lung water, and mortality were measured. alphaENaC mRNA and protein were specifically reduced by approximately 65% after pSi-4 injection. Nedd4-2 mRNA and protein were reduced by approximately 60% after pSi-N1 injection. Interestingly, alphaENaC and betaENaC mRNA and protein expression were increased after Nedd4-2 silencing. Extravascular lung water was significantly increased after alphaENaC silencing and reduced after Nedd4-2 silencing. alphaENaC silencing resulted in a fourfold increase in newborn mortality, whereas silencing Nedd4-2 did not affect mortality. We also isolated distal lung epithelial (DLE) cells after in vivo alphaENaC or Nedd4-2 silencing and measured alphaENaC or Nedd4-2 expression in freshly isolated DLE cells. In these DLE cells, there were attenuated alphaENaC or Nedd4-2 mRNA and protein, thus demonstrating that alphaENaC and Nedd4-2 silencing occurred in alveolar epithelial cells after ttip injection. We also looked for pDNA by PCR to determine pDNA presence in the lungs and found strong evidence for pDNA presence in both lungs. Thus we provide evidence that ENaC and Nedd4-2 are involved in the transition from lung fluid secretion to fluid absorption near term and at birth.
Li Tianbo; Koshy Shyny; Folkesson Hans G
American journal of physiology. Lung cellular and molecular physiology
2007
2007-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajplung.00151.2007" target="_blank" rel="noreferrer noopener">10.1152/ajplung.00151.2007</a>
PKA delivery to the distal lung air spaces increases alveolar liquid clearance after isoproterenol-induced alveolar epithelial PKA desensitization.
Adrenergic beta-Agonists/*pharmacology; Animals; Body Fluids/physiology; Cyclic AMP-Dependent Protein Kinases/*administration & dosage; Desensitization; Extravascular Lung Water/metabolism; Immunologic; Isoproterenol/*pharmacology; Male; Pulmonary Alveoli/cytology/*drug effects/*metabolism; Pulmonary Circulation/physiology; Pulmonary Edema/metabolism; Rats; Respiratory Mucosa/cytology/drug effects/metabolism; Sprague-Dawley
Isoproterenol (Iso) infusion for 48 h in rats decreases the ability of beta-adrenoceptor (beta-AR) agonists to increase alveolar liquid clearance (ALC). An impairment in protein kinase A (PKA) function appears to be critical in producing the desensitized ALC response. To test this hypothesis, we used a novel protein delivery reagent (Chariot, Active Motif) to deliver either the PKA catalytic subunit or the PKA holoenzyme to the distal lung epithelium of Iso-infused rats (400 microg.kg(-1).h(-1), 48 h). After this infusion, ALC was measured by mass balance over 2 h. ALC in Iso-infused rats was 27.9% (SD 5.8) of instilled volume absorbed. Delivery of the catalytic PKA subunit to Iso-infused rats increased ALC to 47.7% (SD 8.9) (P \textless 0.05). ALC in Iso-infused rats delivered the inactive PKA holoenzyme [29.6% (SD 2.5)] was not increased above baseline values. Subsequent holoenzyme activation by intravenous infusion of the stable cAMP analog Sp-8-Bromo-cAMPS increased ALC to 41.7% (SD 8.8) (P \textless 0.05). Immunohistochemical localization of Chariot-delivered PKA revealed staining in the alveolar and distal airway epithelium. These data indicate that protein delivery reagents can be used to rapidly deliver biologically active proteins to the distal lung epithelium and that PKA desensitization may be an important rate-limiting event in the development of Iso-induced desensitization of the alveolar epithelial beta-AR signaling pathway.
Maron Michael B; Folkesson Hans G; Stader Sonya M; Walro Jon M
American journal of physiology. Lung cellular and molecular physiology
2005
2005-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajplung.00134.2004" target="_blank" rel="noreferrer noopener">10.1152/ajplung.00134.2004</a>