EFFECTS IN VIVO OF NEUROHYPOPHYSIAL HORMONES ON THE CONTRACTILE ACTIVITY OF ACCESSORY SEX ORGANS IN MALE RABBITS

Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB ( trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1 −/− animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function.

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Fundamental Roles of Axial Stretch in Isometric and Isobaric Evaluations of Vascular Contractility

Journal of Biomechanical Engineering ◽

10.1115/1.4042171 ◽

2019 ◽

Vol 141 (3) ◽

Cited By ~ 4

Author(s):

Alexander W. Caulk ◽

Jay D. Humphrey ◽

Sae-Il Murtada

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Muscle Function ◽

Contractile Function ◽

Contractile Activity ◽

Comparison Of Methods ◽

Axial Stretch ◽

Smooth Muscle Function ◽

In Vivo Loading

Vascular smooth muscle cells (VSMCs) can regulate arterial mechanics via contractile activity in response to changing mechanical and chemical signals. Contractility is traditionally evaluated via uniaxial isometric testing of isolated rings despite the in vivo environment being very different. Most blood vessels maintain a locally preferred value of in vivo axial stretch while subjected to changes in distending pressure, but both of these phenomena are obscured in uniaxial isometric testing. Few studies have rigorously analyzed the role of in vivo loading conditions in smooth muscle function. Thus, we evaluated effects of uniaxial versus biaxial deformations on smooth muscle contractility by stimulating two regions of the mouse aorta with different vasoconstrictors using one of three testing protocols: (i) uniaxial isometric testing, (ii) biaxial isometric testing, and (iii) axially isometric plus isobaric testing. Comparison of methods (i) and (ii) revealed increased sensitivity and contractile capacity to potassium chloride and phenylephrine (PE) with biaxial isometric testing, and comparison of methods (ii) and (iii) revealed a further increase in contractile capacity with isometric plus isobaric testing. Importantly, regional differences in estimated in vivo axial stretch suggest locally distinct optimal biaxial configurations for achieving maximal smooth muscle contraction, which can only be revealed with biaxial testing. Such differences highlight the importance of considering in vivo loading and geometric configurations when evaluating smooth muscle function. Given the physiologic relevance of axial extension and luminal pressurization, we submit that, when possible, axially isometric plus isobaric testing should be employed to evaluate vascular smooth muscle contractile function.

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A malonyl-CoA fuel-sensing mechanism in muscle: effects of insulin, glucose, and denervation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.269.2.e283 ◽

1995 ◽

Vol 269 (2) ◽

pp. E283-E289 ◽

Cited By ~ 25

Author(s):

A. K. Saha ◽

T. G. Kurowski ◽

N. B. Ruderman

Keyword(s):

Skeletal Muscle ◽

Plasma Insulin ◽

Contractile Activity ◽

High Plasma ◽

Muscle Contractions ◽

Glucose Levels ◽

Malonyl Coa ◽

Ad Libitum ◽

Sciatic Nerve Stimulation

Increases in the concentration of malonyl-CoA in skeletal muscle have been observed in the KKAy mouse, an obese rodent with high plasma insulin and glucose levels [Saha et al. Am. J. Physiol. 267 (Endocrinol. Metab. 30): E95-E101, 1994]. To assess whether insulin and glucose directly regulate malonyl-CoA in muscle, soleus muscles from young rats were incubated with insulin and glucose at various concentrations, and their content of malonyl-CoA was determined. In addition, the effect on malonyl-CoA of denervation and electrically induced muscle contractions was assessed. The concentration of malonyl-CoA in the soleus, taken directly from a rat fed ad libitum, was 2.0 +/- 0.2 nmol/g. In muscles incubated for 20 min in a medium devoid of added insulin and glucose, the concentration was decreased to 0.8 +/- 0.2 nmol/g. When the medium contained 0.5, 7.5, or 30 mM glucose, malonyl-CoA levels were 1.3 +/- 0.1, 1.8 +/- 0.1, or 2.4 +/- 0.2 nmol/g, respectively, in the absence of insulin and 1.7 +/- 0.1, 4.6 +/- 0.3, or 5.5 +/- 0.6 nmol/g in its presence (10 mU/ml). Compared with its level in a control muscle, the concentration of malonyl-CoA was increased threefold in the soleus 6-8 h after denervation and remained twofold higher for > or = 48 h. In contrast, muscle contractions induced by sciatic nerve stimulation, in vivo, acutely decreased the concentration of malonyl-CoA by 30-35%. The results indicate that insulin and glucose, and probably contractile activity, regulate the concentration of malonyl-CoA in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

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Skeletal muscle phenotype signaling with ex vivo endurance-type dynamic contractions in rat muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.00107.2021 ◽

2021 ◽

Author(s):

Jesper Emil Jakobsgaard ◽

Jacob Andresen ◽

Frank V. de Paoli ◽

Kristian Vissing

Keyword(s):

Skeletal Muscle ◽

Translation Initiation ◽

Ex Vivo ◽

Contractile Activity ◽

Specific Protein ◽

Signaling Proteins ◽

Dependent Manner ◽

Metabolic Signaling ◽

Dynamic Endurance

Skeletal muscle phenotype may influence the response sensitivity of myocellular regulatory mechanisms to contractile activity. To examine this, we employed an ex vivo endurance-type dynamic contraction model to evaluate skeletal muscle phenotype-specific protein signaling responses in rat skeletal muscle. Preparations of slow-twitch soleus and fast-twitch extensor digitorum longus skeletal muscle from 4-wk old female Wistar rats were exposed to an identical ex vivo dynamic endurance-type contraction paradigm consisting of 40 minutes of stretch-shortening contractions under simultaneous low-frequency electrostimulation delivered in an intermittent pattern. Phosphorylation of proteins involved in metabolic signaling and signaling for translation initiation was evaluated at 0, 1, and 4 hours after stimulation by immunoblotting. For both muscle phenotypes, signaling related to metabolic events was upregulated immediately after stimulation, with concomitant absence of signaling for translation-initiation. Signaling for translation-initiation was then activated in both muscle phenotypes at 1-4 hours after stimulation, coinciding with attenuated metabolic signaling. The recognizable pattern of signaling responses support how our ex vivo dynamic muscle contraction model can be utilized to infer a stretch-shortening contraction pattern resembling stretch-shortening contraction of in vivo endurance exercise. Moreover, using this model, we observed that some specific signaling proteins adhering to metabolic events or to translation initation exhibited phosphorylation changes in a phenotype-dependent manner, whereas other signaling proteins exhibited phenotype-independent changes. These findings may aid the interpretation of myocellular signaling outcomes adhering to mixed muscle samples collected during human experimental trials.

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Role of prostaglandins in contractile activity of the ampulla of the rabbit oviduct

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1980.238.2.e157 ◽

1980 ◽

Vol 238 (2) ◽

pp. E157-E166 ◽

Cited By ~ 2

Author(s):

M. J. Harper ◽

L. W. Coons ◽

D. A. Radicke ◽

B. J. Hodgson ◽

G. Valenzuela

Keyword(s):

Spontaneous Activity ◽

Contractile Activity ◽

Prostaglandin E ◽

High Dose ◽

Field Stimulation ◽

Prostaglandin Synthetase ◽

Response Curves ◽

Normal Tissues

Contractile activity of the ampulla of rabbit oviducts removed 24 h after an ovulating injection was studied in vitro. Spontaneous activity, field-stimulated activity, and response to phenylephrine were studied in normal, reversed, and scraped (endosalpinx removed) sections of tissues in the presence or absence of inhibitors of prostaglandin synthetase (8 or 51 micrograms/ml indomethacin or 10 or 100 micrograms/ml 5,8,11,14-eicosatetraynoic acid (ETA)). The effects of in vivo treatment with 10 mg/kg of indomethacin on the same responses were examined. Scraped tissues produced more prostaglandin E and F (measured by radioimmunoassay) than did normal tissues, and this production was suppressed by 10 micrograms/ml of indomethacin or 100 micrograms/ml of ETA. Production of prostaglandin by normal tissues was not depressed by these compounds in vitro, but was significantly reduced by pretreatment of the animals with indomethacin in vivo. In the absence of the endosalpinx, the myosalpinx exhibited spontaneous activity and responded to field stimulation and phenylephrine. Scraped and reversed tissues, however, showed a faster decline in response to field stimulation than normal tissues, and this was due to the traumatization. By contrast, traumatization increased the sensitivity of the tissue to respond to phenylephrine. Inhibition of prostaglandin synthetase by low doses of indomethacin or ETA prevented desensitization of the tissue to field stimulation, but this desensitization was little affected by the higher doses of indomethacin in vitro or in vivo. ETA did not affect the phenylephrine dose-response curves and nor did 8 micrograms/ml of indomethacin, whereas the high dose was inhibitory. Spontaneous activity was only affected by the in vivo pretreatment with indomethacin, which prevented the decline in activity of scraped tissue with time.

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Effects of alpha-adrenergic stimuli on mesenteric collecting lymphatics in the rate

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.1.r331 ◽

1997 ◽

Vol 273 (1) ◽

pp. R331-R336 ◽

Cited By ~ 6

Author(s):

J. N. Benoit

Keyword(s):

Smooth Muscle ◽

Stroke Volume ◽

Contractile Activity ◽

Tracking System ◽

Video Tracking ◽

Sprague Dawley ◽

Shortening Velocity ◽

Adrenoceptor Agonist ◽

Lymphatic Pumping

The present study examined the effects of alpha 1- and alpha 2-adrenergic stimuli on rat mesenteric collecting lymphatics in vivo. Sprague-Dawley rats were anesthetized, and the mesentery was prepared for intravital microscopic study. Mesenteric collecting lymphatic diameter was continuously monitored by using a computerized video tracking system, and indexes of lymphatic pumping (e.g., contraction frequency, stroke volume, ejection fraction, and muscle shortening velocity) were determined from the diameter record. Contractile activity was monitored before and during the administration of various adrenergic agonists and antagonists. The receptor antagonists prazosin (alpha 1) and yohimbine (alpha 2) did not significantly alter baseline diameter or contractile activity, which suggests that lymphatics possess no basal adrenergic tone. Norepinephrine and phenylephrine (01-1.0 microM) produced dose-dependent increases in frequency and decreases in diameter. Lymphatic pump flow increased in direct proportion to frequency, because stroke volume did not change. The changes in lymphatic pumping produced by 1 microM norepinephrine were completely blocked by prazosin or phentolamine and only partially blocked by yohimbine. The alpha 2-adrenoceptor agonist (alpha-methyl-norepinephrine) produced no changes in lymphatic activity. This latter observation suggests that a role for postjunctional alpha 2-adrenoceptors in modulating mesenteric lymphatic smooth muscle is unlikely. The results of these studies support the existence of alpha-adrenoceptors on lymphatic smooth muscle. It is concluded that conditions characterized by increased sympathetic outflow may augment lymphatic function through alpha 1- but not alpha 2-adrenoceptors.

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Degranulation enhances release of a stable contractile factor from rabbit polymorphonuclear leukocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.274.5.h1545 ◽

1998 ◽

Vol 274 (5) ◽

pp. H1545-H1551

Author(s):

Justin R. Hamilton ◽

Joanne L. Hart ◽

Owen L. Woodman

Keyword(s):

Slow Rate ◽

Polymorphonuclear Leukocytes ◽

Cytochalasin B ◽

Contractile Activity ◽

90 C 10 ◽

Isolated Aorta ◽

Aortic Contraction ◽

Factor Release

We investigated the release of a stable contractile factor(s) from rabbit isolated polymorphonuclear leukocytes (PMNs; 108cells/ml) incubated in Tyrode buffer at 37°C. PMNs were untreated, stimulated with N-formylmethionyl-leucyl-phenylalanine (FMLP; 0.1 μM), or degranulated with cytochalasin B (1 μM) in combination with FMLP (0.1 μM). Products from unstimulated PMNs incubated for 60 min caused significantly greater contraction of rabbit isolated aorta (0.56 ± 0.12 g, n = 8) than did products released from PMNs during a 5-min incubation (0.32 ± 0.07 g, n = 11, P < 0.05). Stimulation alone did not affect contractile factor release; however, products released from degranulated PMNs caused significantly greater aortic contraction (0.48 ± 0.08 g, n = 5) than products from nondegranulated PMNs (0.24 ± 0.04 g, n = 5, P < 0.05) after a 5-min incubation. The contractile activity of PMN-derived products was virtually abolished by heat (90°C, 10 min) or protease (trypsin; 166 U/ml, 5 h) treatment. These findings suggest a PMN-derived protein vasoconstrictor(s) is spontaneously released at a slow rate in vitro and that degranulation can enhance this rate of release. Because PMN degranulation in vivo is associated with inflammation, these results support suggestions that PMN-derived contractile factors may contribute to the impaired blood flow observed during postischemic reperfusion.

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Antigonadal Activity of the Neurohypophysial Hormones: In Vivo Regulation of Testicular Function of Hypophysectomized Rats1

Biology of Reproduction ◽

10.1095/biolreprod37.4.935 ◽

1987 ◽

Vol 37 (4) ◽

pp. 935-946 ◽

Cited By ~ 5

Author(s):

Eli Y. Adashi ◽

Carol E. Resnick ◽

Barry R. Zirkin

Keyword(s):

Testicular Function ◽

Neurohypophysial Hormones

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A PERFUSED TELEOSTEAN GILL PREPARATION: VASCULAR ACTIONS OF NEUROHYPOPHYSIAL HORMONES AND CATECHOLAMINES

Journal of Endocrinology ◽

10.1677/joe.0.0510621 ◽

1971 ◽

Vol 51 (4) ◽

pp. 621-635 ◽

Cited By ~ 100

Author(s):

J. C. RANKIN ◽

J. MAETZ

Keyword(s):

Adrenergic Receptors ◽

Ringer Solution ◽

Arginine Vasotocin ◽

Millipore Filter ◽

Flow Rates ◽

Alternative Pathways ◽

Neurohypophysial Hormones ◽

Flow Through ◽

Β Adrenergic Receptors

SUMMARY When isolated eel gills were perfused under conditions resembling, as closely as possible, those found in vivo and under constant pressure, neurohypophysial hormones decreased and catecholamines increased the rate of flow of perfusate, the latter response being mediated by β-adrenergic receptors. When the Ringer solution was not filtered before use, flow rates rapidly declined and 10−5 m-adrenaline or noradrenaline was required to maintain constant flow. Under these conditions, 10−14 m-isotocin or 10−13 m-arginine vasotocin (AVT) produced vasoconstriction. When the Ringer solution was filtered through a 0·22 μm Millipore filter before use, constant high flow rates could be maintained in the absence of catecholamines. Noradrenaline increased the flow rate at concentrations of down to 10−9 mol/l, adrenaline being slightly less active when filtered Ringer solution was used. However, the sensitivity to neurohypophysial hormones was considerably reduced, 10−11 to 10−10 m-isotocin and 5 × 10−11 to 5 × 10−10 m-AVT being the lowest concentrations producing vasoconstriction. No difference in sensitivity to neurohypophysial hormones or catecholamines was observed between gills from seawater adapted or freshwater adapted gills. The results are discussed in relation to the alternative pathways of blood flow through the gills.

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