Characterization of optimal resting tension in human pulmonary arteries

Activation of adenylyl cyclase (AC), of which there are 10 diversely regulated isoforms, is important in regulating pulmonary vascular tone and remodeling. Immunohistochemistry in rat lungs demonstrated that AC2, AC3, and AC5/6 predominated in vascular and bronchial smooth muscle. Isoforms 1, 4, 7, and 8 localized to the bronchial epithelium. Exposure of animals to hypoxia did not change the pattern of isoform expression. RT-PCR confirmed mRNA expression of AC2, AC3, AC5, and AC6 and demonstrated AC7 and AC8 transcripts in smooth muscle. Western blotting confirmed the presence of AC2, AC3, and AC5/6 proteins. Functional studies provided evidence of cAMP regulation by Ca2+ and protein kinase C-activated but not Gi-inhibited pathways, supporting a role for AC2 and a Ca2+-stimulated isoform, AC8. However, NKH-477, an AC5-selective activator, was more potent than forskolin in elevating cAMP and inhibiting serum-stimulated [3H]thymidine incorporation, supporting the presence of AC5. These studies demonstrate differential expression of AC isoforms in rat lungs and provide evidence that AC2, AC5, and AC8 are functionally important in cAMP regulation and growth pathways in pulmonary artery myocytes.

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Responses of isolated pulmonary arteries to the C5a anaphylatoxin

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1990.259.5.h1325 ◽

1990 ◽

Vol 259 (5) ◽

pp. H1325-H1329 ◽

Cited By ~ 1

Author(s):

R. E. Crowell ◽

D. E. Van Epps ◽

W. P. Reed

Keyword(s):

Pulmonary Arteries ◽

H1 Receptor ◽

Experimental Conditions ◽

Resting Tension ◽

Several Variables ◽

Muscle Tissues ◽

Anaphylatoxin C5a ◽

Different Response ◽

C5a Anaphylatoxin ◽

H1 Receptor Antagonist

The anaphylatoxin C5a possesses spasmogenic activity in smooth muscle tissues. In this study, we examined the effect of C5a on isolated rabbit pulmonary artery (PA) ring segments under a variety of experimental conditions. C5a (1-100 nM) caused transient constriction of PA at resting tension. C5a-induced PA constriction was not affected by the histamine H1-receptor antagonist pyrilamine (1 microM) but was significantly decreased by the cyclooxygenase inhibitor indomethacin (1 microM). Disruption of the endothelial layer of the vessel had no effect on C5a activity in resting PA. PA, which had been preconstricted with norepinephrine (5 microM), exhibited a different response to C5a than PA at resting tension, however. C5a (1-10 nM) induced a biphasic response in preconstricted PA, initially causing further constriction followed by a greater degree of relaxation resulting in an overall decrease in PA tension. All responses of preconstricted PA to C5a were completely eliminated by indomethacin and significantly depressed by endothelial disruption. These data indicate that C5a interacts directly with isolated rabbit PA, but the nature of the PA response to this peptide depends on several variables including the presence or absence of active PA tension and cyclooxygenase metabolites, and the presence of intact endothelium.

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Responses of isolated pulmonary arteries to synthetic peptide F-Met-Leu-Phe

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.1.h107 ◽

1989 ◽

Vol 257 (1) ◽

pp. H107-H112

Author(s):

R. E. Crowell ◽

D. E. Van Epps ◽

W. P. Reed

Keyword(s):

Smooth Muscle ◽

Pulmonary Artery ◽

Receptor Antagonist ◽

Synthetic Peptide ◽

Pulmonary Arteries ◽

Histamine Receptor ◽

Relaxation Response ◽

Rabbit Pulmonary Artery ◽

Resting Tension ◽

Thromboxane Synthetase

The chemoattractant formyl-methionine-leucine-phenylalanine (FMLP) has recently been shown to possess spasmogenic properties in smooth muscle preparations from various organs. In this study we have investigated the actions of this peptide on isolated rabbit pulmonary artery (PA) ring segments. FMLP stimulated concentration-dependent constriction of PA at resting tension. However, in PA that had been preconstricted by norepinephrine, FMLP stimulated concentration-dependent relaxation. FMLP-stimulated PA constriction was inhibited by earlier exposure to indomethacin or to furegrelate, a thromboxane synthetase inhibitor, but not by earlier exposure to the H1 histamine receptor antagonist pyrilamine. FMLP-stimulated relaxation of PA was totally abolished by indomethacin but not by furegrelate or pyrilamine. Disruption of the endothelium in PA preparations decreased both the constriction and relaxation response to the peptide, suggesting that these cells were involved in these responses. These results indicate that the chemotactic factor FMLP can elicit constriction or relaxation of isolated PA, depending on the underlying active PA tension. In addition, both constriction and relaxation are dependent on cyclooxygenase products and intact endothelium.

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Morphological and functional characterization of the endosarcomeric elastic filament

AJP Cell Physiology ◽

10.1152/ajpcell.1990.259.1.c144 ◽

1990 ◽

Vol 259 (1) ◽

pp. C144-C149 ◽

Cited By ~ 31

Author(s):

G. Salviati ◽

R. Betto ◽

S. Ceoldo ◽

S. Pierobon-Bormioli

Keyword(s):

Electron Microscopy ◽

Functional Characterization ◽

Psoas Muscle ◽

Selective Removal ◽

Skinned Fibers ◽

Thin Filaments ◽

Resting Tension ◽

Thick Filaments ◽

Elastic Filament

The elastic filament was studied in chemically skinned fibers from rabbit psoas muscle by electron microscopy and resting tension measurements. Extraction of skinned fibers with 40 mM sodium pyrophosphate caused a selective removal of about two-thirds of the thick filaments and formed a gap between the remaining portion of the A band and the I band. Very thin filaments were seen in the gap and were decorated by anti-titin antibody. The resting tension of these fibers was comparable to that of unextracted control fibers. When the M band was completely extracted by a solution containing 0.6 M NaCl, the resting tension completely disappeared at sarcomere lengths from 2.8 to approximately 3.4 microns. These results suggest that the elastic force of short sarcomeres is endowed in the titin filaments and that these filaments are anchored to some structures of the Z and M lines. Other filaments were found in the gap between the two I bands of NaCl-extracted sarcomeres. These filaments differed from titin filaments by a larger diameter and the anchoring points. They may represent the sarcomeric structures responsible for the resting tension of extracted fibers stretched at sarcomere lengths longer than 3.4 microns.

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Further characterization of presynaptic β-adrenoceptors in guinea-pig pulmonary arteries

European Journal of Pharmacology ◽

10.1016/0014-2999(83)90480-6 ◽

1983 ◽

Vol 91 (2-3) ◽

pp. 287-290 ◽

Cited By ~ 19

Author(s):

Yoshimi Misu ◽

Misako Kuwahara ◽

Masayoshi Kaiho ◽

Takao Kubo

Keyword(s):

Guinea Pig ◽

Pulmonary Arteries

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Characterization of agonist-induced vasoconstriction in mouse pulmonary artery

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00968.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. H220-H228 ◽

Cited By ~ 13

Author(s):

Minlin Xu ◽

Oleksandr Platoshyn ◽

Ayako Makino ◽

Wolfgang H. Dillmann ◽

Katerina Akassoglou ◽

...

Keyword(s):

Vascular Reactivity ◽

Molecular Mechanisms ◽

Electromechanical Coupling ◽

Pulmonary Arteries ◽

Pulmonary Vasculature ◽

Pulmonary Vascular Disease ◽

Transgenic Mouse Models ◽

Vascular Responsiveness ◽

Coupling Mechanisms

In recent years, transgenic mouse models have been developed to examine the underlying cellular and molecular mechanisms of lung disease and pulmonary vascular disease, such as asthma, pulmonary thromboembolic disease, and pulmonary hypertension. However, there has not been systematic characterization of the basic physiological pulmonary vascular reactivity in normal and transgenic mice. This represents an intellectual “gap”, since it is important to characterize basic murine pulmonary vascular reactivity in response to various contractile and relaxant factors to which the pulmonary vasculature is exposed under physiological conditions. The present study evaluates excitation- and pharmacomechanical-contraction coupling in pulmonary arteries (PA) isolated from wild-type BALB/c mice. We demonstrate that both pharmaco- and electromechanical coupling mechanisms exist in mice PA. These arteries are also reactive to stimulation by α1-adrenergic agonists, serotonin, endothelin-1, vasopressin, and U-46619 (a thromboxane A2 analog). We conclude that the basic vascular responsiveness of mouse PA is similar to those observed in PA of other species, including rat, pig, and human, albeit on a different scale and to varying amplitudes.

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A role for actin polymerization in persistent pulmonary hypertension of the newborn

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2014-0413 ◽

2015 ◽

Vol 93 (3) ◽

pp. 185-194 ◽

Cited By ~ 4

Author(s):

Jena Fediuk ◽

Shyamala Dakshinamurti

Keyword(s):

Pulmonary Hypertension ◽

Actin Polymerization ◽

Pulmonary Arteries ◽

Persistent Pulmonary Hypertension ◽

Vascular Relaxation ◽

Cortical Actin ◽

Actin Isoform ◽

Pulmonary Arterial

Persistent pulmonary hypertension of the newborn (PPHN) is defined as the failure of normal pulmonary vascular relaxation at birth. Hypoxia is known to impede postnatal disassembly of the actin cytoskeleton in pulmonary arterial myocytes, resulting in elevation of smooth muscle α-actin and γ-actin content in elastic and resistance pulmonary arteries in PPHN compared with age-matched controls. This review examines the original histological characterization of PPHN with attention to cytoskeletal structural remodeling and actin isoform abundance, reviews the existing evidence for understanding the biophysical and biochemical forces at play during neonatal circulatory transition, and specifically addresses the role of the cortical actin architecture, primarily identified as γ-actin, in the transduction of mechanical force in the hypoxic PPHN pulmonary circuit.

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