Inhibition of hypoxic pulmonary vasoconstriction by antagonists of store-operated Ca2+ and nonselective cation channels

2005 ◽  
Vol 289 (1) ◽  
pp. L5-L13 ◽  
Author(s):  
Letitia Weigand ◽  
Joshua Foxson ◽  
Jian Wang ◽  
Larissa A. Shimoda ◽  
J. T. Sylvester
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Pulmonary Arteries ◽  
Cation Channels ◽  
Pulmonary Vasoconstriction ◽  
Nonselective Cation Channels ◽  
Pressor Responses ◽  
Intracellular Ca ◽  
Pulmonary Arterial

Previous studies indicated that acute hypoxia increased intracellular Ca2+ concentration ([Ca2+]i), Ca2+ influx, and capacitative Ca2+ entry (CCE) through store-operated Ca2+ channels (SOCC) in smooth muscle cells from distal pulmonary arteries (PASMC), which are thought to be a major locus of hypoxic pulmonary vasoconstriction (HPV). Moreover, these effects were blocked by Ca2+-free conditions and antagonists of SOCC and nonselective cation channels (NSCC). To test the hypothesis that in vivo HPV requires CCE, we measured the effects of SOCC/NSCC antagonists (SKF-96365, NiCl2, and LaCl3) on pulmonary arterial pressor responses to 2% O2 and high-KCl concentrations in isolated rat lungs. At concentrations that blocked CCE and [Ca2+]i responses to hypoxia in PASMC, SKF-96365 and NiCl2 prevented and reversed HPV but did not alter pressor responses to KCl. At 10 μM, LaCl3 had similar effects, but higher concentrations (30 and 100 μM) caused vasoconstriction during normoxia and potentiated HPV, indicating actions other than SOCC blockade. Ca2+-free perfusate and the voltage-operated Ca2+ channel (VOCC) antagonist nifedipine were potent inhibitors of pressor responses to both hypoxia and KCl. We conclude that HPV required influx of Ca2+ through both SOCC and VOCC. This dual requirement and virtual abolition of HPV by either SOCC or VOCC antagonists suggests that neither channel provided enough Ca2+ on its own to trigger PASMC contraction and/or that during hypoxia, SOCC-dependent depolarization caused secondary activation of VOCC.

Hypoxic constriction of porcine distal pulmonary arteries: endothelium and endothelin dependence

2001 ◽  
Vol 280 (5) ◽  
pp. L856-L865 ◽  
Author(s):  
Q. Liu ◽  
J. S. K. Sham ◽  
L. A. Shimoda ◽  
J. T. Sylvester
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Bronchial Arteries ◽  
Pulmonary Vasoconstriction ◽  
Endothelial Denudation ◽  
Basal Release ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle

To determine the role of endothelium in hypoxic pulmonary vasoconstriction (HPV), we measured vasomotor responses to hypoxia in isolated seventh-generation porcine pulmonary arteries < 300 μm in diameter with (E+) and without endothelium. In E+ pulmonary arteries, hypoxia decreased the vascular intraluminal diameter measured at a constant transmural pressure. These constrictions were complete in 30–40 min; maximum at Po 2 of 2 mmHg; half-maximal at Po 2 of 40 mmHg; blocked by exposure to Ca2+-free conditions, nifedipine, or ryanodine; and absent in E+ bronchial arteries of similar size. Hypoxic constrictions were unaltered by indomethacin, enhanced by indomethacin plus N G-nitro-l-arginine methyl ester, abolished by BQ-123 or endothelial denudation, and restored in endothelium-denuded pulmonary arteries pretreated with 10−10 M endothelin-1 (ET-1). Given previous demonstrations that hypoxia caused contractions in isolated pulmonary arterial myocytes and that ET-1 receptor antagonists inhibited HPV in intact animals, our results suggest that full in vivo expression of HPV requires basal release of ET-1 from the endothelium to facilitate mechanisms of hypoxic reactivity in pulmonary arterial smooth muscle.

Role of thromboxane A2-activated nonselective cation channels in hypoxic pulmonary vasoconstriction of rat

2012 ◽  
Vol 302 (1) ◽  
pp. C307-C317 ◽  
Author(s):  
Hae Young Yoo ◽  
Su Jung Park ◽  
Eun-Young Seo ◽  
Kyung Sun Park ◽  
Jung-A. Han ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Cation Channels ◽  
Pcr Analysis ◽  
Transient Receptor Potential Vanilloid ◽  
Pulmonary Vasoconstriction ◽  
Nonselective Cation Channels

Hypoxia-induced pulmonary vasoconstriction (HPV) is critical for matching of ventilation/perfusion in lungs. Although hypoxic inhibition of K+ channels has been a leading hypothesis for depolarization of pulmonary arterial smooth muscle cells (PASMCs) under hypoxia, pharmacological inhibition of K+ channels does not induce significant contraction in rat pulmonary arteries. Because a partial contraction by thromboxane A2 (TXA2) is required for induction of HPV, we hypothesize that TXA2 receptor (TP) stimulation might activate depolarizing nonselective cation channels (NSCs). Consistently, we found that 5–10 nM U46619, a stable agonist for TP, was indispensible for contraction of rat pulmonary arteries by 4-aminopyridine, a blocker of voltage-gated K+ channel (Kv). Whole cell voltage clamp with rat PASMC revealed that U46619 induced a NSC current ( INSC,TXA2) with weakly outward rectifying current-voltage relation. INSC,TXA2 was blocked by ruthenium red (RR), an antagonist of the transient receptor potential vanilloid-related channel (TRPV) subfamily. 2-Aminoethoxydiphenyl borate, an agonist for TRPV1–3, consistently activated NSC channels in PASMCs. In contrast, agonists for TRPV1 (capsaicin), TRPV3 (camphor), or TRPV4 (α-PDD) rarely induced an increase in the membrane conductance of PASMCs. RT-PCR analysis showed the expression of transcripts for TRPV2 and -4 in rat PASMCs. Finally, it was confirmed that pretreatment with RR largely inhibited HPV in the presence of U46619. The pretreatment with agonists for TRPV1 (capsaicin) and TRPV4 (α-PDD) was ineffective as pretone agents for HPV. Taken together, it is suggested that the concerted effects of INSC,TXA2 activation and Kv inhibition under hypoxia induce membrane depolarization sufficient for HPV. TRPV2 is carefully suggested as the TXA2-activated NSC in rat PASMC.

Acute hypoxia increases intracellular [Ca2+] in pulmonary arterial smooth muscle by enhancing capacitative Ca2+ entry

2005 ◽  
Vol 288 (6) ◽  
pp. L1059-L1069 ◽  
Author(s):  
Jian Wang ◽  
Larissa A. Shimoda ◽  
Letitia Weigand ◽  
Wenqian Wang ◽  
Dejun Sun ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Primary Cultures ◽  
Fluorescent Microscopy ◽  
Pulmonary Arteries ◽  
Arterial Smooth Muscle ◽  
Fura 2 ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle

Hypoxic pulmonary vasoconstriction (HPV) requires influx of extracellular Ca2+ in pulmonary arterial smooth muscle cells (PASMCs). To determine whether capacitative Ca2+ entry (CCE) through store-operated Ca2+ channels (SOCCs) contributes to this influx, we used fluorescent microscopy and the Ca2+-sensitive dye fura-2 to measure effects of 4% O2 on intracellular [Ca2+] ([Ca2+]i) and CCE in primary cultures of PASMCs from rat distal pulmonary arteries. In PASMCs perfused with Ca2+-free Krebs Ringer bicarbonate solution (KRBS) containing cyclopiazonic acid to deplete Ca2+ stores in sarcoplasmic reticulum and nifedipine to prevent Ca2+ entry through L-type voltage-operated Ca2+ channels (VOCCs), hypoxia markedly enhanced both the increase in [Ca2+]i caused by restoration of extracellular [Ca2+] and the rate at which extracellular Mn2+ quenched fura-2 fluorescence. These effects, as well as the increased [Ca2+]i caused by hypoxia in PASMCs perfused with normal salt solutions, were blocked by the SOCC antagonists SKF-96365, NiCl2, and LaCl3 at concentrations that inhibited CCE >80% but did not alter [Ca2+]i responses to 60 mM KCl. In contrast, the VOCC antagonist nifedipine inhibited [Ca2+]i responses to hypoxia by only 50% at concentrations that completely blocked responses to KCl. The increased [Ca2+]i caused by hypoxia was completely reversed by perfusion with Ca2+-free KRBS. LaCl3 increased basal [Ca2+]i during normoxia, indicating effects other than inhibition of SOCCs. Our results suggest that acute hypoxia enhances CCE through SOCCs in distal PASMCs, leading to depolarization, secondary activation of VOCCs, and increased [Ca2+]i. SOCCs and CCE may play important roles in HPV.

Responses of isolated guinea pig pulmonary venules to hypoxia and anoxia

1989 ◽  
Vol 67 (5) ◽  
pp. 2147-2153 ◽  
Author(s):  
W. R. Tracey ◽  
J. T. Hamilton ◽  
I. D. Craig ◽  
N. A. Paterson
Keyword(s):  
Guinea Pig ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Major Site ◽  
Sustained Contraction ◽  
Pulmonary Vasoconstriction ◽  
Ph Dependent

Because small pulmonary arteries are believed to be the major site of hypoxic pulmonary vasoconstriction (HPV), pulmonary venular responses to hypoxia have received little attention. Therefore the responses of isolated guinea pig pulmonary venules to hypoxia (bath PO2, 25 Torr) and anoxia (bath PO2, 0 Torr) were characterized. Pulmonary venules [effective lumen radius (ELR), 116 +/- 2 microns] with an adherent layer of parenchyma responded to hypoxia and anoxia with a graded sustained contraction (hypoxia, 0.03 +/- 0.01; anoxia, 0.26 +/- 0.03 mN/mm), whereas paired femoral venules (ELR, 184 +/- 7 microns) contracted to anoxia only (0.05 +/- 0.02 mN/mm). Repeated challenges with hypoxia and anoxia continued to elicit sustained pulmonary venular contractions; femoral venule contractions to anoxia were not repeatable. Hypoxia- and anoxia-induced pulmonary venular contractions were calcium and pH dependent. Dissection of the parenchyma from pulmonary venules did not alter contractions to decreased PO2. Anoxic contractions of pulmonary venules were variably reduced by replacement of the bath fluid; however, the release of a contractile mediator(s) from pulmonary venules during hypoxia or anoxia was not demonstrated. Pulmonary venular responses to hypoxia and anoxia are similar to those induced by hypoxia in vivo, and results obtained from this model may be useful in predicting mechanisms of HPV.

Hypoxic Pulmonary Vasoconstriction

2012 ◽  
Vol 92 (1) ◽  
pp. 367-520 ◽  
Author(s):  
J. T. Sylvester ◽  
Larissa A. Shimoda ◽  
Philip I. Aaronson ◽  
Jeremy P. T. Ward
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vessels ◽  
Pulmonary Vasoconstriction ◽  
Neonatal Life ◽  
High Altitude Pulmonary Edema ◽  
Alveolar Hypoxia ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle ◽  
Isolated Lungs

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.

scholarly journals Role of ASIC1 in the development of chronic hypoxia-induced pulmonary hypertension

2014 ◽  
Vol 306 (1) ◽  
pp. H41-H52 ◽  
Author(s):  
Carlos H. Nitta ◽  
David A. Osmond ◽  
Lindsay M. Herbert ◽  
Britta F. Beasley ◽  
Thomas C. Resta ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Chronic Hypoxia ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Pulmonary Arteries ◽  
Systolic Pressure ◽  
Arterial Remodeling ◽  
Ventricular Systolic Pressure ◽  
Intracellular Ca

Chronic hypoxia (CH) associated with respiratory disease results in elevated pulmonary vascular intracellular Ca2+ concentration, which elicits enhanced vasoconstriction and promotes vascular arterial remodeling and thus has important implications in the development of pulmonary hypertension (PH). Store-operated Ca2+ entry (SOCE) contributes to this elevated intracellular Ca2+ concentration and has also been linked to acute hypoxic pulmonary vasoconstriction (HPV). Since our laboratory has recently demonstrated an important role for acid-sensing ion channel 1 (ASIC1) in mediating SOCE, we hypothesized that ASIC1 contributes to both HPV and the development of CH-induced PH. To test this hypothesis, we examined responses to acute hypoxia in isolated lungs and assessed the effects of CH on indexes of PH, arterial remodeling, and vasoconstrictor reactivity in wild-type (ASIC1+/+) and ASIC1 knockout (ASIC1−/−) mice. Restoration of ASIC1 expression in pulmonary arterial smooth muscle cells from ASIC1−/− mice rescued SOCE, confirming the requirement for ASIC1 in this response. HPV responses were blunted in lungs from ASIC1−/− mice. Both SOCE and receptor-mediated Ca2+ entry, along with agonist-dependent vasoconstrictor responses, were diminished in small pulmonary arteries from control ASIC−/− mice compared with ASIC+/+ mice. The effects of CH to augment receptor-mediated vasoconstrictor and SOCE responses in vessels from ASIC1+/+ mice were not observed after CH in ASIC1−/− mice. In addition, ASIC1−/− mice exhibited diminished right ventricular systolic pressure, right ventricular hypertrophy, and arterial remodeling in response to CH compared with ASIC1+/+ mice. Taken together, these data demonstrate an important role for ASIC1 in both HPV and the development of CH-induced PH.

Desflurane Inhibits Hypoxic Pulmonary Vasoconstriction in Isolated Rabbit Lungs

1995 ◽  
Vol 83 (3) ◽  
pp. 552-556. ◽  
Author(s):  
Stephan A. Loer ◽  
Thomas W. L. Scheeren ◽  
Jorg Tarnow
Keyword(s):  
Minimum Alveolar Concentration ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Constant Flow ◽  
Inhibiting Effect ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
Inspiratory Oxygen

Background Inhalational anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV) in vivo and in vitro with a half-maximum inhibiting effect (ED50) within concentrations applied for general anesthesia. Because it is unknown whether desflurane acts likewise, we studied its effect on HPV in isolated blood-perfused rabbit lungs and compared its ED50 with that of halothane. Methods Isolated blood-perfused rabbit lungs were randomly allocated to treatment with either desflurane (n = 6) or halothane (n = 6). HPV, defined as an increase in pulmonary arterial pressure (PAP) at constant flow, was elicited by decreasing inspiratory oxygen concentration from 20% to 3% for 4 min. This effect was determined without (control HPV) and with increasing concentrations of the anesthetics (fraction of inspired carbon dioxide kept constant at 4.8 +/- 0.2%, perfusate temperature at 37 degrees C, and blood flow at 100 ml.min-1). Results Before exposure to the anesthetics, PAP increased by 8.6 +/- 1.9 cmH2O for all lungs within 4 min of hypoxia (control PAP for all lungs 19.6 +/- 2.5 cmH2O). Desflurane decreased this effect in a concentration-dependent fashion with an ED50 of 14.5%, compared with that of halothane, with an ED50 of 1.7%. Conclusions Assuming that 1 minimum alveolar concentration (MAC) values of desflurane and halothane for rabbits are 8.9% and 1.39%, respectively, this study yields ED50 values for the inhibition of HPV of approximately 1.6 MAC for desflurane and 1.2 MAC for halothane (P not statistically significant).

Abstract 658: Suppressed Hypoxic Pulmonary Vasoconstriction in Malonyl-CoA-Decarboxylase Knock-Out Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Gopinath Sutendra ◽  
Sebastien Bonnet ◽  
Alois Haromy ◽  
Gary Lopaschuk ◽  
Jason Dyck ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Exercise Tolerance ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Metabolic Enzyme ◽  
Acid Oxidation ◽  
Wild Mice ◽  
Pulmonary Vasoconstriction ◽  
Malonyl Coa ◽  
Intracellular Ca

Background : Hypoxic pulmonary vasoconstriction (HPV) is intrinsic to the pulmonary artery smooth muscle cells (PASMC). A recently proposed mechanism for HPV suggests that hypoxia is sensed within the mitochondria, altering the production of activated oxygen species (AOS) in response to changes in PO 2 . Decreased AOS (like H 2 O 2 ) inhibit Kv channels, depolarize PASMC, increase influx of Ca ++ , causing PASMC contraction. Malonyl-CoA-Decarboxylase (MCD) is a metabolic enzyme, that when inhibited suppresses the mitochondrial-based fatty acid oxidation, promoting glucose oxidation. We have shown that knockout mice lacking MCD (KO-MCD) are resistant to chronic-hypoxia-induced pulmonary hypertension (CH-PHT) but they have a normal phenotype in normoxia. We hypothesized that KO-MCD mice have suppressed HPV. Methods and Results : We compared KO-MCD to wild mice (W-MCD) using PASMC patch clamping, intracellular Ca ++ (fura-2), mitochondrial membrane potential (ΔΨm, using TMRM and confocal microscopy), mitochondrial AOS production (mitosox and confocal microscopy) and isolated intact resistance PA rings; we also studied exercise tolerance (distance covered in a treadmill) during normoxia and acute hypoxia (n =7–10 mice/group for all studies). As expected, in W-MCD mice acute hypoxia inhibited K + current (Ik), increased intracellular Ca ++ and mitochondrial ΔΨm, decreased mitochondrial AOS production, increased PA tone and decreased exercise tolerance (due to the rapid increase in PA pressure and decrease in cardiac output). In contrast, KO-MCD showed an impressive lack of response to acute hypoxia in all the parameters studied (table ). Conclusions : Our data show that acute hypoxia is not sensed in W-MCD mice and might offer at least a partial explanation for the resistance to CH-PHT in these mice. They also offer a novel insight into the metabolic basis of pulmonary vascular reactivity and HPV.

scholarly journals Pulmonary vasodilation by acetazolamide during hypoxia: impact of methyl-group substitutions and administration route in conscious, spontaneously breathing dogs

2014 ◽  
Vol 116 (7) ◽  
pp. 715-723 ◽  
Author(s):  
Philipp A. Pickerodt ◽  
Roland C. Francis ◽  
Claudia Höhne ◽  
Friederike Neubert ◽  
Stella Telalbasic ◽  
...  
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Administration Routes ◽  
Pulmonary Vasodilation ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction ◽  
Thiadiazole Ring ◽  
Pulmonary Arterial ◽  
Isolated Lungs ◽  
Spontaneously Breathing

Acetazolamide (ACZ) prevents hypoxic pulmonary vasoconstriction (HPV) in isolated lungs, animals, and humans, but not by carbonic anhydrase (CA) inhibition. We studied administration routes in, and certain structural aspects of, ACZ critical to HPV inhibition. Analogs of ACZ during acute hypoxia were tested in unanesthetized dogs. Dogs breathed normoxic gas for 1 h (inspired O2 fraction = 0.21), followed by 10% O2 for 2 h (hypoxia) in these protocols: 1) controls; 2) ACZ intravenously (2 mg·kg−1·h−1); 3) ACZ orally (5 mg/kg, 12 and 1 h before the experiment); 4) inhaled ACZ (750 mg); 5) methazolamide (MTZ) intravenously (3 mg·kg−1·h−1); and 6) N-methyl-acetazolamide (NMA) intravenously (10 mg·kg−1·h−1). In controls, mean pulmonary arterial pressure (MPAP) increased 7 mmHg, and pulmonary vascular resistance (PVR) 224 dyn·s·cm−5 with hypoxia ( P < 0.05). With intravenous and inhaled ACZ, MPAP and PVR did not change during hypoxia. With oral ACZ, HPV was only slightly suppressed; MPAP increased 5 mmHg and PVR by 178 dyn·s·cm−5 during hypoxia. With MTZ and NMA, the MPAP rise (4 ± 2 mmHg) was reduced, and PVR did not increase during hypoxia compared with normoxia (MTZ intravenous: 81 ± 77 and 68 ± 82 dyn·s·cm−5 with NMA intravenous). Inhaled ACZ prevents HPV, but not without causing systemic CA inhibition. NMA, a compound lacking CA inhibiting effects by methylation at the sulfonamide moiety, and MTZ, a CA-inhibiting analog methylated at the thiadiazole ring, are only slightly less effective than ACZ in reducing HPV.

beta-Adrenergic mechanisms attenuated hypoxic pulmonary vasoconstriction during systemic hypoxia in cats

1994 ◽  
Vol 266 (5) ◽  
pp. H1777-H1785 ◽  
Author(s):  
M. Shirai ◽  
T. Shindo ◽  
I. Ninomiya
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Internal Diameter ◽  
Television System ◽  
Autonomic Nervous ◽  
Pulmonary Vasoconstriction ◽  
Alveolar Hypoxia

In this study, we examined how locally mediated hypoxic pulmonary vasoconstriction is modulated by autonomic nervous system activation during global alveolar hypoxia (GAH) accompanied by systemic hypoxemia. Using an X-ray television system on the in vivo cat lung, we measured changes in the internal diameter (ID) during GAH and regional alveolar hypoxia (RAH) without systemic hypoxemia in identical small pulmonary arteries and veins (100-600 microns ID). We also analyzed the effects of the autonomic nervous system blockade on the hypoxic ID changes. During GAH the ID of the arteries reduced by 5 +/- 1 and 3 +/- 1% with 10 and 5% O2 inhalations, respectively, whereas during RAH the arterial ID reduced by 12 +/- 1 and 18 +/- 1% with 10 and 5% O2 inhalations, respectively. The magnitude of the ID reduction was significantly smaller during GAH than during RAH. After pretreatment with propranolol, however, GAH induced large ID reductions (16 +/- 1 and 23 +/- 1% with 10 and 5% O2 inhalations) with patterns very similar to those seen during RAH. Phentolamine and atropine had no effect on the response during GAH. The ID reductions during RAH, on the other hand, were unaffected by all the blockers. The results indicate that, in the cat, alveolar hypoxia per se acts locally to constrict the small pulmonary vessels and that the hypoxic vasoconstriction is attenuated by a beta-receptor-mediated vasodilator effect during GAH with systemic hypoxemia. In addition, we found that, after adrenalectomy plus ganglion blockade with hexamethonium bromide, the GAH-induced ID reduction with 5% O2 inhalation was enhanced from 3 to 19%.(ABSTRACT TRUNCATED AT 250 WORDS)

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