Red Blood Cells Play a Crucial Role in Maintaining Vascular Reactivity to Hypoxia in Isolated Rat Lungs

McMurtry, Ivan F.; Hookway, B. W.; Roos, S. D.

doi:10.1378/chest.71.2_supplement.253

Cited by 24 publications

(12 citation statements)

References 8 publications

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“…Several previous studies have indicated that red blood cells (RBCs) play a role as an oxygen sensor because the HPV was augmented when lungs were perfused with blood [16] and affected by hematocrit level [22]. In this study, we also confirmed that RBCs augment the HPV in rabbit lungs (Fig.…”

Section: Introductionsupporting

confidence: 86%

Luminal ATP-induced contraction of rabbit pulmonary arteries and role of purinoceptors in the regulation of pulmonary arterial pressure

Baek

Yoo

Park

et al. 2008

Pflugers Arch - Eur J Physiol

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The effects of luminal ATP between rabbit pulmonary (PAs) and coronary arteries (CAs) were compared to understand the role of purinoceptors in the regulation of pulmonary arterial pressure (PAP) under hypoxia. Diameters of vessels were video analyzed under luminal perfusion. ATP-induced membrane currents and intracellular Ca(2+) signals ([Ca(2+)](i)) were compared in pulmonary (PASMCs) and coronary myocytes (CASMCs) using patch clamp and spectrofluorimetry. PAP was measured in perfused lungs under ventilation. Luminal ATP induced constriction of rabbit PAs in the presence of endothelium. In contrast, CAs showed dilating responses to luminal ATP even in the absence of endothelium. In PASMCs, both P2X-mediated inward current and P2Y-mediated store Ca(2+) release were consistently observed. In contrast, CASMCs showed neither P2X nor P2Y responses. In the perfused lungs, hypoxia-induced PAP increase was decreased by suramin, a purinergic antagonist. A luminal application of alpha,beta-meATP largely increased PAP, whereas UTP decreased PAP. The combined application of P2X- and P2Y-selective agonists (alpha,beta-meATP and UTP) increased PAP. However, the perfusion of ATP alone decreased PAP, and the ATP-induced PAP decrease was affected neither by adenosine receptor antagonist nor by nitric oxide synthase inhibitor. In summary, although the luminal ATP constricts isolated PAs and suramin attenuated the HPV of perfused lungs, the bimodal responses of PAP to purinergic agonists indicate that the luminal ATP regulates pulmonary circulation via complex signaling interactions in situ.

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Section: Introductionsupporting

confidence: 86%

Luminal ATP-induced contraction of rabbit pulmonary arteries and role of purinoceptors in the regulation of pulmonary arterial pressure

Baek

Yoo

Park

et al. 2008

Pflugers Arch - Eur J Physiol

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“…[21446667] When whole blood was applied in the perfusate, the amplitude of HPV increased more than two-fold, potentially because of the increase in viscosity or presence of vasoreactive molecules in blood,[2123426869] although the absolute amplitude of HPV or alveolar hypoxia-induced increase in PAP was still small (Fig. 3).…”

Section: Discussionmentioning

confidence: 99%

“…[41011161718192021] The pioneering studies identifying the role of Ca 2+ in HPV were conducted by McMurtry et al[22232425] in the 1970s using isolated rat lungs. Studies conducted in isolated cells or vessels provide valuable information about the response of individual proteins or genes in specific cell types.…”

mentioning

confidence: 99%

Optimization of Isolated Perfused/Ventilated Mouse Lung to Study Hypoxic Pulmonary Vasoconstriction

Yoo¹,

Zeifman²,

Ko³

et al. 2013

Pulm. circ.

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Hypoxic pulmonary vasoconstriction (HPV) is a compensatory physiological mechanism in the lung that optimizes the matching of ventilation to perfusion and thereby maximizes gas exchange. Historically, HPV has been primarily studied in isolated perfused/ventilated lungs; however, the results of these studies have varied greatly due to different experimental conditions and species. Therefore, in the present study, we utilized the mouse isolated perfused/ventilated lung model for investigation of the role of extracellular Ca2+ and caveolin-1 and endothelial nitric oxide synthase expression on HPV. We also compared HPV using different perfusate solutions: Physiological salt solution (PSS) with albumin, Ficoll, rat blood, fetal bovine serum (FBS), or Dulbecco's Modified Eagle Medium (DMEM). After stabilization of the pulmonary arterial pressure (PAP), hypoxic (1% O2) and normoxic (21% O2) gases were applied via a ventilator in five-minute intervals to measure HPV. The addition of albumin or Ficoll with PSS did not induce persistent and strong HPV with or without a pretone agent. DMEM with the inclusion of FBS in the perfusate induced strong HPV in the first hypoxic challenge, but the HPV was neither persistent nor repetitive. PSS with rat blood only induced a small increase in HPV amplitude. Persistent and repetitive HPV occurred with PSS with 20% FBS as perfusate. HPV was significantly decreased by the removal of extracellular Ca2+ along with addition of 1 mM EGTA to chelate residual Ca2+ and voltage-dependent Ca2+ channel blocker (nifedipine 1 μM). PAP was also reactive to contractile stimulation by high K+ depolarization and U46619 (a stable analogue of thromboxane A2). In summary, optimal conditions for measuring HPV were established in the isolated perfused/ventilated mouse lung. Using this method, we further confirmed that HPV is dependent on Ca2+ influx.

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“…HPV was more vigorous and persistent in isolated rat lungs if blood, plasma plus erythrocytes, or physiological salt solution plus erythrocytes were used as perfusate rather than physiological salt solution or plasma (1244,1245). Salutory effects of erythrocytes on HPV were also seen in intact dogs (949) and isolated lungs of rats, cats, rabbits, and ferrets, but not pigs (379, 712,1120,2057,2091,2137).…”

Section: Sources Of Variationmentioning

confidence: 98%

Hypoxic Pulmonary Vasoconstriction

Sylvester

Shimoda

Aaronson

et al. 2012

Physiological Reviews

607

621

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It has been known for more than 60 years, and suspected for over 100, that alveolar hypoxia causes pulmonary vasoconstriction by means of mechanisms local to the lung. For the last 20 years, it has been clear that the essential sensor, transduction, and effector mechanisms responsible for hypoxic pulmonary vasoconstriction (HPV) reside in the pulmonary arterial smooth muscle cell. The main focus of this review is the cellular and molecular work performed to clarify these intrinsic mechanisms and to determine how they are facilitated and inhibited by the extrinsic influences of other cells. Because the interaction of intrinsic and extrinsic mechanisms is likely to shape expression of HPV in vivo, we relate results obtained in cells to HPV in more intact preparations, such as intact and isolated lungs and isolated pulmonary vessels. Finally, we evaluate evidence regarding the contribution of HPV to the physiological and pathophysiological processes involved in the transition from fetal to neonatal life, pulmonary gas exchange, high-altitude pulmonary edema, and pulmonary hypertension. Although understanding of HPV has advanced significantly, major areas of ignorance and uncertainty await resolution.

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Red Blood Cells Play a Crucial Role in Maintaining Vascular Reactivity to Hypoxia in Isolated Rat Lungs

Cited by 24 publications

References 8 publications

Luminal ATP-induced contraction of rabbit pulmonary arteries and role of purinoceptors in the regulation of pulmonary arterial pressure

Luminal ATP-induced contraction of rabbit pulmonary arteries and role of purinoceptors in the regulation of pulmonary arterial pressure

Optimization of Isolated Perfused/Ventilated Mouse Lung to Study Hypoxic Pulmonary Vasoconstriction

Hypoxic Pulmonary Vasoconstriction

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