Isoform Shift Research Articles

Tension production and thin-filament protein isoforms in developing rat myocardium.

The calcium sensitivity of tension production and the expression of troponin I (TnI) and troponin T (TnT) isoforms in skinned neonatal (7 days after birth) and adult rat myocardium were determined. Isometric tension was measured after activation at a known resting sarcomere length in ventricular trabeculae at adult and, for the first time, neonatal ages. Analysis of the tension-pCa relationships indicates a greater calcium sensitivity (approximately 0.3 pCa units) in neonatal ventricular trabeculae compared with adult trabeculae. The maximal isometric tension-generating ability (i.e., tension-tissue cross-sectional area) is threefold greater in adult compared with neonatal trabeculae. Developmental transitions in TnI and TnT isoform expression in atrial and ventricular tissue were examined simultaneously and were found to be dissimilar. Shifts in the expression of TnT isoforms precede shifts in TnI isoforms in ventricular tissue. The opposite pattern occurs in atrial tissue, with shifts in TnI preceding those in TnT. The results show that the greater calcium sensitivity of neonatal compared with adult rat ventricular tissue is associated with developmental changes in both TnT and TnI isoform expressions. These isoform expression patterns may facilitate myocardial tension production at the neonatal stage, when the tension-generating ability of individual trabeculae is much lower than that in the adult.

Contractility and myosin heavy chain isoform patterns in developing tracheal muscle

Changes in airway smooth muscle reactivity with development may be caused by either modification of the excitation-contraction coupling system or alteration of the contractile apparatus. The mechanism responsible for the reported changes in reactivity was addressed in this study by examining airway smooth muscle contractility and myosin heavy chain isoform patterns as a function of post-neonatal development. Changes in length and force, in response to supramaximal electrical stimulation, were recorded simultaneously as functions of time for tracheal smooth muscle (TSM) strips from 8-week-old and 25-week-old male rabbits. Both the passive and active length-tension (L-T) curves as well as the force-velocity (F-V) curves for the two age groups of rabbit TSM were not significantly different indicating no changes in contractility during post-neonatal development in rabbits. This conclusion is surprising in light of reports of myosin heavy chain (MHC) isoform shifts in porcine trachealis during comparable periods of development. Therefore, MHC isoform ratios were compared by sodium dodecyl sulfate-polyacrylimide gel electrophoresis for tracheal smooth muscle from male rabbits of 8 and 25 weeks of age. Unlike the reported MHC isoform shifts in the pig tracheal muscle, the rabbit trachealis showed no difference in MHC isoform ratios between the two age groups compared in this study. In conclusion, no changes occur in contractility or MHC isoform patterns during post-neonatal development of rabbit tracheal smooth muscle. Therefore, reported changes in airway muscle reactivity are likely due to changes in receptors or in second messenger systems rather than to changes in the contractile apparatus.

Effects of oestrogen treatment on serum gonadotrophin bioactivity, immunoreactivity and isohormone distribution, and on immunoreactive inhibin levels, in prostatic cancer patients

No data are available on effects of long-term exposure to oestrogen on bioactivity of gonadotrophins in men. We studied the effects of a 6-month oestrogen therapy on serum FSH and LH bioactivity (B), immunoreactivity (I) and isohormone distribution, and on serum I-inhibin levels, in patients with prostatic carcinoma. Eleven men with advanced prostatic cancer were studied, each receiving 160 mg of polyoestradiol phosphate (Estradurin) once a month intramuscularly for 6 months. Serum samples were collected before, and after 2 and 6 months of oestrogen treatment. Serum B- and I-FSH levels were measured by immature rat granulosa cell bioassay and immunofluorometric (IFMA, Delfia) assay, respectively, and those of B- and I-LH by mouse interstitial cell bioassay and IFMA, respectively. Serum oestradiol (E2) concentrations were measured by IFMA assay, and serum testosterone (T) and inhibin levels by radioimmunoassay. Isoelectric focusing was used for fractionation of the FSH and LH isoforms. The pretreatment levels of B-FSH and I-FSH were 84.7 +/- 21.6 and 11.4 +/- 3.2 IU/l (mean +/- SEM), respectively, and the B/I ratio of FSH was 8.3 +/- 1.0. The pretreatment levels of B-LH and I-LH were 23.5 +/- 3.2 and 10.1 +/- 2.3 IU/l, respectively, and the B/I ratio was 3.0 +/- 0.4. After 6 months of oestrogen therapy, B-FSH and I-FSH decreased to 37.5 +/- 8.1 (P < 0.05) and 1.3 +/- 0.3 IU/l (P < 0.01), respectively, but the B/I ratio of FSH increased to 28.5 +/- 4.2 (P < 0.05). B- and I-LH levels decreased in 6 months to 7.4 +/- 0.9 and 2.3 +/- 0.5 IU/l (P < 0.01), respectively, but no change was found in the B/I ratio of LH. Serum T levels decreased from 19.0 +/- 2.6 to 2.7 +/- 0.9 nmol/l (P < 0.01) during the 6-month treatment, and the respective E2 levels increased from 0.2 +/- 0.01 to 4.4 +/- 0.5 nmol/l (P < 0.01). Serum I-inhibin levels were analysed from eight patients. The levels at 0, 2 and 6 months were 0.81 +/- 0.09, 0.50 +/- 0.03 and 0.54 +/- 0.01 microgram/l, respectively. Gonadotrophins in the pretreatment and 6-month samples of four patients were analysed by isoelectric focusing. In FSH of all subjects, and in LH of three subjects, a shift from acidic to more basic isoforms occurred after oestrogen therapy. This is in keeping with the increase of the B/I ratio of FSH. With LH, the isoform shift occurred between fractions with similar B/I ratios, and hence there was no shift in the overall B/I ratio. Oestrogen therapy of men suppressed bioactive and immunoreactive levels of gonadotrophins. The B/I ratio of FSH increased, and this increase was associated with a shift in the isohormone profile to more basic forms. In contrast, no change occurred in the B/I ratio of LH, even though changes in the isohormone profile were observed. Hence, not all changes in the isohormone distribution of gonadotrophins result in changes of the intrinsic in-vitro bioactivity.

Role of environmental conditions on the expression levels, glycoform pattern and levels of sialyltransferase for hFSH produced by recombinant CHO cells

A recombinant CHO cell line in which the expression of human follicle stimulating hormone (hFSH) was under the control of the beta actin promoter was maintained in steady state perfusion cultures on a protein free medium. The level of expression of the hFSH was controlled by varying the steady state level of dissolved oxygen (10-90% of air saturation) and of sodium butyrate (0-1.5mM). Under these conditions, the specific productivity of hFSH (qFSH) varied from 0.7 to 4.8 ng hFSH/10(6) cells/h. As the specific productivity of hFSH increased, there was a shift in the FSH isoforms to the lower pI fractions, corresponding to increased sialic acid content. As the specific productivity of hFSH increased, shifting the isoform distribution towards the lower pI isoforms, that the sialyltransferase enzymic activity also increased.

An additional carbohydrate chain in the variant thyroxine-binding globulin-Gary (TBGAsn-96) impairs its secretion.

The T4-binding globulin-Gary (TBG-G) variant has severely impaired T4 binding, is unstable at 37 C, and presents an apparent anodal shift of all isoforms when submitted to isoelectric focusing. Inheritance of this abnormal TBG produces a profound decrease in the serum levels of native TBG with reciprocal changes in its denatured form, causing thyroid hormone concentrations to be as low as those found in complete TBG deficiency. The TBG-G gene possesses a single nucleotide substitution replacing the normal IIe96 (ATC) with Asn (AAC), thus creating a new site for N-linked glycosylation. In order to determine whether TBG-G contains an additional carbohydrate chain as indirectly suggested by the isoelectric focusing results, cDNAs containing the normal TBG (TBG-N), and TBG-G were inserted in the appropriate vectors to allow their expression in mammalian cells (COS-1) and in amphibian (Xenopus) oocytes. In both systems, expression of TBG-G yielded a larger molecule than TBG-N when analyzed by polyacrylamide gel electrophoresis under denaturing conditions. However, both were identical in size when synthesized in COS-1 cells in the presence of tunicamycin or when deglycosylated after their synthesis in Xenopus oocytes. Pulse chase experiments revealed impaired secretion and excessive overall intracellular degradation of TBG-G relative to TBG-N. As expected from studies on serum from affected subjects, in vitro expressed TBG-G had a 10-fold lower affinity for T4. These studies prove that the new site for potential glycosylation created by the point mutation in TBG-G is indeed glycosylated.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification and functional significance of troponin I isoforms in neonatal rat heart myofibrils.

We investigated the mechanism(s) responsible for differences in the effects of acidic pH on Ca2+ activation of the activity of adult and neonatal rat heart myofilaments. Studies on preparations of myofilaments reconstituted with adult troponin-tropomyosin (Tn-Tm) and either adult or neonatal thick filaments indicated that the difference in effect of acidic pH is related to differences in Tn-Tm and not other myofilament proteins. Immunoblotting analysis showed that development of the rat heart myofibrils is associated with isoform switching from slow skeletal TnI to cardiac TnI and from a slow mobility isoform of TnT (TnT1) to a faster Mr isoform (TnT2. Expression of slow skeletal TnI was associated with a relative insensitivity of myofilament Ca2+ activation to deactivation by acidic pH. Moreover, the effect of acidic pH on Ca2+ activation of ATPase activity of soleus myofibrils, which contain cardiac TnC and slow skeletal TnI, was essentially the same as the effect of acidic pH on rat cardiac myofibrils in the early neonatal period. Neonatal myofilaments also contained a relative abundance of a set of polypeptides copurifying with the thin filaments. We have identified these proteins as histones. The relative amount of histones among a variety of preparations from different species was not correlated with the pH sensitivity of myofibrillar Ca2+ activation. Shifts in TnT isoforms among these species were also not correlated with an altered response to acidic pH. Our data provide evidence in support of the hypothesis that the relative insensitivity of neonatal myofilament activity to acidic pH is due to the presence of slow skeletal TnI in the thin-filament regulatory complex.

Effect of sodium deprivation on cardiac hypertrophy in spontaneously hypertensive rats: Influence of aging

Sodium has been identified as a causal factor in the development of hypertension in experimental animal models as well as in clinical human subjects. Sodium is also known to play a role in modulating myocardial mass and its pattern of myosin isozyme distribution. In the rodent model, the accumulation of V 3 myosin isozyme (MI), due to the modulating influence of sodium, has been shown to be associated with persistent cardiac hypertrophy and heart failure. In this paper, we have examined the effect of the restriction of dietary sodium on blood pressure, ventricular weight and myosin isoforms in spontaneously hypertensive rats (SHR) and the relationship of these parameters with age. In 10- to 11-week-old SHR, dietary sodium restriction for 14 weeks resulted in a significant reduction in ventricular mass associated with systolic shifting of myosin isoform from V 3 type to V 1 type with no change in systolic blood pressure level; dietary sodium restriction also showed a significant reduction in body weight. When the effect of dietary sodium restriction (for 8 weeks) was studied in relation to age (in 11-, 16- and 24-week-old rats) a significant shift in myosin isoform from the V 3 to the V 1 type was noted in the 11-week-old rats; a slight but significant shift was noted in 16-week-old rats, and no change in myosin isoform distribution was noted in the 24-week-old SHR. The alteration in myosin isoform and myocardial mass in the 11- and 16-week-old rats was independent of changes in systolic blood pressure. This study demonstrates that sodium plays an important role not only in modulating myocardial mass but also in changing the biochemical composition of the heart. This study also suggests that in genetic hypertension, the restriction of sodium at a very young age may fully prevent the development of hypertension and hypertrophy. However, the mechanism by which the sodium ion modulates myocardial mass and the expression of either V 1 or V 3 myosin genes is unknown; the question of how sodium affects the cardiac function also remains. Some evidence suggests that sympathetic outflow may play an important role, but further studies are needed to validate this.

Analysis of Physiological Data Characterized by Two Regimes Separated by an Abrupt Transition

Previous articleNext article No AccessTechnical CommentsAnalysis of Physiological Data Characterized by Two Regimes Separated by an Abrupt TransitionRonald G. Duggleby and Leigh C. WardRonald G. Duggleby Search for more articles by this author and Leigh C. Ward Search for more articles by this author PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Volume 64, Number 3May - Jun., 1991 Article DOIhttps://doi.org/10.1086/physzool.64.3.30158213 Views: 3Total views on this site Citations: 7Citations are reported from Crossref Journal History This article was published in Physiological Zoology (1928-1998), which is continued by Physiological and Biochemical Zoology (1999-present). Copyright 1991 The University of ChicagoPDF download Crossref reports the following articles citing this article:Vincent J. Caiozzo, Heather Richmond, Serge Kaska, Dahlia Valeroso The mechanical behavior of activated skeletal muscle during stretch: effects of muscle unloading and MyHC isoform shifts, Journal of Applied Physiology 103, no.44 (Oct 2007): 1150–1160.https://doi.org/10.1152/japplphysiol.00469.2006Haruka Wada, Thomas P. Hahn, Creagh W. Breuner Development of stress reactivity in white-crowned sparrow nestlings: Total corticosterone response increases with age, while free corticosterone response remains low, General and Comparative Endocrinology 150, no.33 (Feb 2007): 405–413.https://doi.org/10.1016/j.ygcen.2006.10.002 Nicola J. Mitchell and Roger S. Seymour The Effects of Nest Temperature, Nest Substrate, and Clutch Size on the Oxygenation of Embryos and Larvae of the Australian Moss Frog, Bryobatrachus nimbus N. J. Mitchell and R. S. Seymour, Physiological and Biochemical Zoology 76, no.11 (Jul 2015): 60–71.https://doi.org/10.1086/345486Carlos A. Jaramillo Response of tropical vegetation to Paleogene warming, Paleobiology 28, no.22 (Jun 2002): 222–243.https://doi.org/10.1666/0094-8373(2002)028&lt;0222:ROTVTP&gt;2.0.CO;2L Ward, B H Cornish, N I Paton, B J Thomas Multiple frequency bioelectrical impedance analysis: a cross-validation study of the inductor circuit and Cole models, Physiological Measurement 20, no.44 (Sep 1999): 333–347.https://doi.org/10.1088/0967-3334/20/4/301LEIGH WARD, NIGEL FULLER, BRUCE CORNISH, MARINOS ELIA, BRIAN THOMAS A Comparison of the Siconolfi and Cole-Cole Procedures for Multifrequency Impedance Data Analysis, Annals of the New York Academy of Sciences 873, no.1 ELECTRICAL BI1 ELECTRICAL BI (Apr 1999): 370–373.https://doi.org/10.1111/j.1749-6632.1999.tb09485.xB H Cornish, L C Ward Data analysis in multiple-frequency bioelectrical impedance analysis, Physiological Measurement 19, no.22 (Jan 1999): 275–283.https://doi.org/10.1088/0967-3334/19/2/014

Actin and myosin isoforms in gallbladder smooth muscle following cholesterol feeding in prairie dogs

Gallbladder smooth muscle contractility decreases after high-cholesterol feeding in prairie dogs. This decrease is not associated with alterations in the total amounts of the contractile proteins actin and myosin. The present study was designed to determine if cholesterol feeding results in alterations in the isoforms of actin and/or myosin heavy chain in gallbladder smooth muscle. Control prairie dogs were fed a trace-cholesterol diet and test animals were fed a high (1.2 %)-cholesterol diet for 8 days. Although the proportion of β-actin was unchanged, the proportion of α-actin in the gallbladder was less in the animals fed the high-cholesterol diet (32.6% ± 1.5% in the control animals and 24.6% ± 0.4% in the diet animals). On the other hand, the proportion of γ-actin was significantly greater in the cholesterol-fed animals. There were no significant differences in the proportions of the myosin heavy-chain isoforms between the two groups. Also, there was no change in the volume fraction of smooth muscle in the gallbladders from the two groups. Thus, cholesterol feeding induces a shift in actin isoforms at the same time that there is a decrease in contractility. Whether the altered pattern of actin isoforms is related to the functional changes remains to be determined.

Effects of age on myosin and creatine kinase isoforms in left ventricles of fischer 344 rats

Left ventricles of hearts from male Fischer 344 rats of 2, 8 and 23 months of age were analyzed to determine if aging results in significant alterations in the isoform distribution of myosin and creatine kinase protein and mRNAs. Left ventricles of maturing (2-month) rats contained almost exclusively α-myosin heavy chain (MHC) mRNA and protein. In adults (8 months) there was a 5-fold increase in β-MHC (fetal isoform) and an approximate 10% decrease in α-MHC mRNA levels, relative to 2 months. By 23 months (senescence), β-MHC mRNA levels had increased by 11-fold and α-MHC mRNA levels had decreased by about 30%. These changes corresponded to an increase in the relative proportion of β-MHC protein, from undetectable levels at 2 months, to about 40% by 8 months and to about 60% by 23 months. Increased levels of β-MHC and its mRNA in older rats correlated with decreased serum thyroid hormone levels. The specific activity of creatine kinase in crude homogenates decreased with age, as has been reported previously. Relative to 2-month controls, the specific activity of creatine kinase had decreased by 21% at 8 months and by 37% at 23 months. Analysis of creatine kinase activity showed no large increase in levels of the fetal (B) isoform with age, as was found for myosin. Levels of mRNAs encoding the B and M isoforms of creatine kinase were significantly reduced in senescent rats. Thus, the decreased levels of creatine kinase in aging rats is correlated with decreased levels of mRNA encoding the BCK and MCK isoforms but not an isoform shift.

Cardiac physiology, biochemistry and morphology in response to excess growth hormone in the rat

The cardiac effects of excess growth hormone (GH) were studied in the intact adult rat and in tissues prepared from the rat. Female Wistar-Furth rats were inoculated with a clonal cell line of pituitary cells which secrete GH. Five weeks later, heart weight had increased 37% compared to control ( P < 0.01) due to concomitant increases in left and right ventricular weight. Hemodynamic measurements in the anesthetized rat showed that GH stimulated rats had a decrease in blood pressure and heart rate and a small increase of left ventricular end-diastolic pressure ( P < 0.05). Measurement of left ventricular contractility and relaxation, and response to β-adrenergic stimulation were decreased in GH compared to control ( P < 0.05). Contractile protein biochemistry showed an 18% reduction in Ca 2+-myosin ATPase activity of the left ventricle ( P < 0.05) and non-denaturing pyrophosphate gels of purified myosin demonstrated a significant shift of isoforms from the exclusive V 1 pattern to both V 1 and V 3 isomyosins in both ventricles ( P < 0.05). In contrast to the physiological and protein biochemistry adaptations, left ventricular morphology by light microscopy and ultrastructure by electron microscopy were normal in the GH stimulated heart. There were no significant changes in myofibril fraction, in the myofibril to mitochondria ratio or in the capillary numerical density of the hypertrophied left ventricle ( P = n.s.). This study demonstrates that under prolonged and extreme stimulation by GH, the heart undergoes considerable growth/hypertrophy. although cardiac morphology remains normal during this growth, there are alterations of the isomyosins such that ATPase activity is diminished and ventricular function is decreased.

Modulation of serum follicle-stimulating hormone bioactivity and isoform distribution by estrogenic steroids in normal women and in gonadal dysgenesis.

To determine the influence of estrogenic steroids on serum FSH bioactivity (B) and immunoreactivity (I) and the FSH isoform distribution profiles, we studied normal women during ovulatory menstrual cycles and a patient with gonadal dysgenesis treated with diethylstilbestrol (DES). Four women with ovulatory menstrual cycles, as judged from their serum immunoreactive LH, FSH, progesterone, and estradiol profiles in daily blood samples, had a significant increase in the mean FSH B/I ratio (P less than 0.05) during the midcycle phase of their menstrual cycles. Similarly, in the patient with gonadal dysgenesis the FSH B/I ratio rose significantly (P less than 0.05) after 3 weeks of DES treatment and declined during the posttreatment period. In five additional normal women, serum obtained during the follicular, midcycle, and luteal phases of their menstrual cycles was chromatofocused, and the FSH isoform distribution pattern determined. Sera obtained from the patient with gonadal dysgenesis before, during, and after DES administration were pooled and studied similarly. Chromatofocusing of a human pituitary tumor extract allowed for determination of the FSH B/I ratio in different pH ranges. The highest FSH B/I ratio was found in the more basic fractions (pH range 5.6-6.0) compared to the acidic fractions. During both the midcycle phase of the normal cycles and the DES administration period in the studies of the patient with gonadal dysgenesis, there was a shift of the FSH isoforms (as measured by immunoassay) to the basic pH range. In contrast, the mid- to late luteal phase samples, which had low B/I ratios, had an increase in FSH isoforms in the acidic pH range (less than 4.8). Similarly, in the patient with gonadal dysgenesis FSH isoforms in the basic range were more abundant during the DES treatment period than in the pre- or posttreatment serum pools. Therefore, it appears that endogenous and exogenous estrogenic stimulation alters FSH isoform distribution such that FSH isoforms that are more basic and have increased biological activity are secreted.

Developmental and functional adaptation of contractile proteins in cardiac and skeletal muscles.

The goal of this review is to summarize our knowledge of the plasticity of striated muscles in terms of contractile proteins. During development or when the working conditions are changed, the intrinsic physiological properties of both cardiac and skeletal muscles are modified. These modifications generally adapt the muscle to the new environmental requirements. One of the best examples is compensatory overload obtained in fast skeletal muscle by synergistic tenotomy and in a fast ventricle, such as in rats, by aortic banding. In both cases, after a few weeks the initial speed of shortening for the unloaded muscle drops, whereas the maximum tension developed remains unchanged. Heat measurements show that efficiency (i.e., g work/mol ATP) is improved at the fiber level. The fast skeletal muscle becomes slow, fatigue resistant, and then more adapted to endurance. For the ventricle as a whole to become slow is beneficial only if one contraction is considered; however, it is detrimental in terms of cardiac output and leads finally to failure. This adaptational process is partly explained by quantitative and qualitative changes in contractile proteins. Protein synthesis is rapidly enhanced and muscles hypertrophy, which in turn multiplies the contractile units and for the cardiac cylinder normalizes the wall stress. In the meantime the structure and, for myosin, the biological activity of several contractile proteins are modified. These modifications are very unlikely to be posttranscriptional and are in fact explained by several isoform shifts. In both tissues, for example, the expression of the gene coding for a fast myosin (MHCf in skeletal muscle, alpha-MHC in ventricles) is repressed and that of the gene coding for a slow myosin (beta-MHC in both tissues) is stimulated. This is accompanied by a coordinated increase in synthesis of other contractile proteins and, in skeletal muscle only, by isoform shifts of myosin light chains and of the TM-TN regulatory system. Other changes are less well understood. During development it has recently been discovered that three different MHCs (MHCemb, MHCneo, and MHCf) appear sequentially in fast skeletal muscle, which explains, for example, several contradictions of immunological cross-reactions. Currently, however, the functional significance of this finding is unknown, and the well-known decrease of shortening velocity observed in cardiac and skeletal muscles during fetal life is unexplained in terms of contractile proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Denervated skeletal muscle displays discoordinate regulation for the synthesis of several myofibrillar proteins.

Synthesis patterns of myosin heavy- and light-chain isoforms, tropomyosin and troponin, have been studied in chicken fast muscle denervated at both neonatal and adult stages. Denervated neonatal muscle does not synthesize the adult myosin heavy-chain isoform at the time of denervation, but it does synthesize the adult isoform several months after denervation. Thus, innervation does not appear to be necessary for the normal sequential replacement of embryonic and neonatal myosin heavy chain by the adult variant. Nerve is required, however, for the regulation of tropomyosin and troponin expression. Normally the pectoralis major muscle represses synthesis of both beta-tropomyosin and leg-type troponin T during late embryonic development. After denervation, however, the muscle relaxes its ongoing repression of these proteins and significant amounts of both beta-tropomyosin and leg-type troponin T are synthesized by the muscle. Denervation also results in an altered pattern of myosin light-chain synthesis so that the ratio of fast light-chain 3/fast light-chain 1 decreases. Similar results are found in muscle denervated at the adult stage. In denervated muscle, therefore, synthesis of these myofibrillar proteins is not coordinated: ongoing isoform shifts proceed to express an adult pattern of myosin heavy chain while tropomyosin, troponin, and myosin light-chain patterns appear to revert to embryonic configurations.

Influences of Po2 and pH on resting and active tensions of pulmonary arterial strips.

ARTICLESInfluences of Po2 and pH on resting and active tensions of pulmonary arterial stripsT. C. Lloyd JrT. C. Lloyd JrPublished Online:01 Jun 1967https://doi.org/10.1152/jappl.1967.22.6.1101MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByAcidosis abolishes the effect of repeated applications of ATP on pulmonary artery force and [Ca2+]iRespiratory Physiology & Neurobiology, Vol. 141, No. 2Effects of changes in pH and CO2 on pulmonary arterial wall tension are not endothelium dependentMichèle Sweeney, David Beddy, Valerie Honner, Bridget Sinnott, Ronan G. O’Regan, and Paul McLoughlin1 December 1998 | Journal of Applied Physiology, Vol. 85, No. 6Myosin isoform shifts and decreased reactivity in hypoxia-induced hypertensive pulmonary arterial muscleC. S. Packer, J. E. Roepke, N. H. Oberlies, and R. A. Rhoades1 May 1998 | American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 274, No. 5Hypoxic and embolic pulmonary vasoconstrictionGeneral Pharmacology: The Vascular System, Vol. 14, No. 1Relaxant responses of the isolated guinea-pig left pulmonary artery produced by acidic histamine solutionsEuropean Journal of Pharmacology, Vol. 70, No. 2Functional studies of the small pulmonary arteriesMicrovascular Research, Vol. 15, No. 1The pulmonary interstitial compartment and the mediator of hypoxic pulmonary vasoconstrictionMicrovascular Research, Vol. 15, No. 1Hypoxia on the pulmonary circulation. How and where it acts.Circulation Research, Vol. 38, No. 4Hypoxia-sensitive neuro-epithelial bodies intrapulmonary secretory neuroreceptors, modulated by the CNSZeitschrift f�r Zellforschung und Mikroskopische Anatomie, Vol. 145, No. 4Role of Histamine in Hypoxic Pulmonary Hypertension in the RatCirculation Research, Vol. 22, No. 3 More from this issue > Volume 22Issue 6June 1967Pages 1101-1109 Copyright & PermissionsCopyright © 1967 the American Physiological Societyhttps://doi.org/10.1152/jappl.1967.22.6.1101PubMed4290841History Published online 1 June 1967 Published in print 1 June 1967 Metrics