Nifedipine does not impede clenbuterol-stimulated muscle hypertrophy.

The mechanism(s) responsible for beta2-adrenergic receptor-mediated skeletal muscle and cardiac hypertrophy remains undefined. This study examined whether calcium influx through L-type calcium channels contributed to the development of cardiac and skeletal muscle (plantaris; gastrocnemius; soleus) hypertrophy during an 8-day treatment with the beta2-adrenergic receptor agonist clenbuterol. Concurrent blockade of L-type calcium channels with nifedipine did not reverse the hypertrophic action of clenbuterol. Moreover, nifedipine treatment alone resulted in both cardiac and soleus muscle hypertrophy (6% and 7%, respectively), and this effect was additive to the clenbuterol-mediated hypertrophy in the heart and soleus muscles. The hypertrophic effects of nifedipine were not associated with increases in total beta-adrenergic receptor density, nor did nifedipine reverse clenbuterol-mediated beta-adrenergic receptor downregulation in either the left ventricle or soleus muscle. Both nifedipine and clenbuterol-induced hypertrophy increased total protein content of the soleus and left ventricle, with no change in protein concentration. In conclusion, our results support the hypothesis that beta2-adrenergic receptor agonist-induced muscle hypertrophy is mediated by mechanisms other than calcium influx through L-type calcium channels.     

Prolonged treadmill training increases HSP70 in skeletal muscle but does not affect age-related functional deficits

Skeletal muscle atrophy and weakness are major causes of frailty in the elderly. Functional deficits in muscles of old humans and rodents are associated with attenuated production of heat shock proteins (HSPs) after exercise, and transgenic overexpression of HSP70 reverses this functional decline. We hypothesized that training would increase HSP70 content of muscle in adult and old wild-type mice and that this would protect against the development of age-related functional deficits. A 10-wk treadmill training protocol at 15 m/min, for 15 min, 3 days/wk resulted in a significant increase in HSP70 content of muscles of adult mice. Muscles of old untrained mice demonstrated a significant increase in HSP70 protein content and a reduction in HSP70 mRNA content compared with adult untrained mice. Training for 12 mo starting at age 12-14 mo old or for 10 wk starting from age 24 mo old resulted in modification of HSP70 protein and mRNA content to levels of adult mice. Training did not change force generation of extensor digitorum longus muscles of old mice or improve recovery after damaging contractions. The twofold increase in HSP70 content in muscles of adult mice after training may have not been sufficient to provide protection in this instance.     

Exercise does not alter subcellular localization, but increases phosphorylation of insulin-signaling proteins in human skeletal muscle

The subcellular localization of insulin signaling proteins is altered by various stimuli such as insulin, insulin-like growth factor I, and oxidative stress and is thought to be an important mechanism that can influence intracellular signal transduction and cellular function. This study examined the possibility that exercise may also alter the subcellular localization of insulin signaling proteins in human skeletal muscle. Nine untrained males performed 60 min of cycling exercise (approximately 67% peak pulmonary O2 uptake). Muscle biopsies were sampled at rest, immediately after exercise, and 3 h postexercise. Muscle was fractionated by centrifugation into the following crude fractions: cytosolic, nuclear, and a high-speed pellet containing membrane and cytoskeletal components. Fractions were analyzed for protein content of insulin receptor, insulin receptor substrate (IRS)-1 and -2, p85 subunit of phosphatidylinositol 3-kinase, Akt, and glycogen synthase kinase-3 (GSK-3). There was no significant change in the protein content of the insulin signaling proteins in any of the crude fractions after exercise or 3 h postexercise. Exercise had no significant effect on the phosphorylation of IRS-1 Tyr612 in any of the fractions. In contrast, exercise increased (P < 0.05) the phosphorylation of Akt Ser473 and GSK-3alpha/beta Ser9/21 in the cytosolic fraction only. In conclusion, exercise can increase phosphorylation of downstream insulin signaling proteins specifically in the cytosolic fraction but does not result in changes in the subcellular localization of insulin signaling proteins in human skeletal muscle. Change in the subcellular protein localization is therefore an unlikely mechanism to influence signal transduction pathways and cellular function in skeletal muscle after exercise.     

Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women

Men and women with hyperandrogenemia have a more proatherogenic plasma lipid profile [e.g., greater triglyceride (TG) and total and low-density lipoprotein-cholesterol and lower high-density lipoprotein-cholesterol concentrations] than healthy premenopausal women. Furthermore, castration of male rats markedly reduces testosterone availability below normal and decreases plasma TG concentration, and testosterone replacement reverses this effect. Testosterone is, therefore, thought to be an important regulator of plasma lipid homeostasis. However, little is known about the effect of testosterone on plasma TG concentration and kinetics. Furthermore, testosterone is a potent skeletal muscle protein anabolic agent in men, but its effect on muscle protein turnover in women is unknown. We measured plasma lipid concentrations, hepatic very low density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 secretion rates, and the muscle protein fractional synthesis rate in 10 obese women before and after trandermal testosterone (1.25 g of 1% AndroGel daily) treatment for 3 wk. Serum total and free testosterone concentrations increased (P < 0.05) by approximately sevenfold in response to testosterone treatment, reaching concentrations that are comparable to those in women with hyperandrogenemia, but lower than the normal range for eugonadal men. Except for a small (～10%) decrease in plasma high-density lipoprotein particle and cholesterol concentrations (P < 0.04), testosterone therapy had no effect on plasma lipid concentrations, lipoprotein particle sizes, and hepatic VLDL-TG and VLDL-apolipoprotein B-100 secretion rates (all P > 0.05); the muscle protein fractional synthesis rate, however, increased by ～45% (P < 0.001). We conclude that testosterone is a potent skeletal muscle protein anabolic agent, but not an important regulator of plasma lipid homeostasis in obese women.     

Adrenergic, nitrergic and peptidergic innervation of the urethral muscle in the boar

In this study, the innervation of the urethral muscle in adult male pigs was investigated using combined NADPH-diaphorase (NADPH-d) histochemistry and immunocytochemistry. Nerve fibres supplying the urethral muscle were found to show NADPH-d activity and they also expressed immunoreactivity to catecholamine synthesising enzymes including tyrosine hydoxylase (TH) and dopamine-beta-hydroxylase (DbetaH) as well as to: vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). Different subpopulations of the nerve fibres (NADPH-d positive, TH-, DbetaH-, VIP- and NPY-immunoreactive (IR), but also NADPH-d/VIP- and NADPH-d/NPY-IR) were disclosed. These nerve fibres were observed not only to run among muscle fibres of the urethral muscle, but also within extrinsic nerve trunks. Moreover, in the organ studied, numerous ganglia were found. The intramural ganglia, composed of a few to 30 neurons were located in the proximal, middle and distal regions of the pelvic urethra. In the vicinity of the urethral muscle, there were mainly small ganglia containing two to several neurons, but also larger ganglia consisting of up to tens neurons were encountered in the connective tissue surrounding the pelvic urethra. In the ganglia observed in the neighbourhood of the urethral muscle, different subpopulations of nerve cells were found, namely: catecholaminergic, nitrergic, VIP-IR, NPY-IR and also NADPH-d/DbetaH-, NADPH-d/VIP- and NADPH-d/NPY-positive. Possible sources of the innervation for this muscle were also discussed.     

Low tryptophan diet increases stress-sensitivity, but does not affect habituation in rats

Cerebral dysfunction of 5-HT (serotonin) has been associated with stress response and with affective disorders. Stress alone is insufficient to induce depression, since only a minor proportion of subjects that have experienced stressful life events develop depressive episodes. We investigated whether long-term brain 5-HT depletion induced in rats by a diet with low content of its precursor tryptophan affects stress-responsiveness in rats. Stress-sensitivity was measured through various physiological parameters and by measuring the rats' response to acoustic stimuli. One group of rats was subjected to daily acoustic stimulus sessions for 5 days. Other groups received both immobilization stress and acoustic stimulus sessions daily for either 9 days (chronic experiment) or 1 day (acute experiment). A low tryptophan diet led to decreases in plasma tryptophan levels, low ratio of tryptophan/large neutral amino acid, whole blood 5-HT, and neuronal 5-HT content in the Dorsal and Median Raphe Nuclei, as well as altered c-fos expression in the brain. Without concomitant immobilization, the diet alone did not affect reactivity and habituation to acoustic stimuli, although plasma corticosterone levels, but not the adrenal weights, were increased on day 5. Low tryptophan and chronic immobilization stress together with the acoustic testing procedure increased adrenal weight, plasma corticosterone levels and reactivity to the acoustic stimuli, but not the rate of habituation to acoustic stimuli. These results show that cerebral dysfunction of serotonin achieved through a low tryptophan diet, increases the sensitivity of rats to external and stressful stimuli, but does not impair the capacity to adapt to these stimuli. Accordingly, brain-serotonin modulates reactivity to stress, but not stress coping.     

Ghrelin increases the motivation to eat, but does not alter food palatability

Homeostatic eating cannot explain overconsumption of food and pathological weight gain. A more likely factor promoting excessive eating is food reward and its representation in the central nervous system (CNS). The anorectic hormones leptin and insulin reduce food reward and inhibit related CNS reward pathways. Conversely, the orexigenic gastrointestinal hormone ghrelin activates both homeostatic and reward-related neurocircuits. The current studies were conducted to identify in rats the effects of intracerebroventricular ghrelin infusions on two distinct aspects of food reward: hedonic valuation (i.e., "liking") and the motivation to self-administer (i.e., "wanting") food. To assess hedonic valuation of liquid food, lick motor patterns were recorded using lickometry. Although ghrelin administration increased energy intake, it did not alter the avidity of licking (initial lick rates or lick-cluster size). Several positive-control conditions ruled out lick-rate ceiling effects. Similarly, when the liquid diet was hedonically devalued with quinine supplementation, ghrelin failed to reverse the quinine-associated reduction of energy intake and avidity of licking. The effects of ghrelin on rats' motivation to eat were assessed using lever pressing to self-administer food in a progressive-ratio paradigm. Ghrelin markedly increased motivation to eat, to levels comparable to or greater than those seen following 24 h of food deprivation. Pretreatment with the dopamine D1 receptor antagonist SCH-23390 eliminated ghrelin-induced increases in lever pressing, without compromising generalized licking motor control, indicating a role for D1 signaling in ghrelin's motivational feeding effects. These results indicate that ghrelin increases the motivation to eat via D1 receptor-dependent mechanisms, without affecting perceived food palatability.     

Raising P50 increases tissue PO2 in canine skeletal muscle but does not affect critical O2 extraction ratio

Curtis, Scott E., Thomas A. Walker, W. E. Bradley, andStephen M. Cain. Raising P₅₀increases tissue PO₂ in canineskeletal muscle but does not affect criticalO₂ extraction ratio.J. Appl. Physiol. 83(5):1681-1689, 1997.Affinity of hemoglobin (Hb) forO₂ determines in part the rate ofO₂ diffusion from capillaries tomyocytes by altering capillary PO₂.We hypothesized that a decrease in HbO₂ affinity (increasedP₅₀) would increase capillary and tissue PO₂(Pti_O2) andimprove O₂ consumption duringischemia. To test this hypothesis, blood flow to the pump-perfused lefthindlimb of 18 anesthetized and paralyzed dogs was progressively decreased over 90 min while hindlimb O₂ consumption andO₂ delivery (O₂)and Pti_O2 weremeasured at the muscle surface. Arterial PO₂ was maintained at 150 ± 10 Torr in all dogs. We increased P₅₀by 12.3 ± 0.9 (SE) Torr in nine dogs with RSR-13, an allosteric modifier of Hb. This decreased arterialO₂ saturation to 90-92% butincreased meanPti_O2 from 35.5 ± 11.6 to 44.1 ± 15.2 (SD) Torr(P < 0.05) with no change incontrols (n = 9).O₂ extraction ratio at criticalO₂was 74 ± 2% in controls and 79 ± 1% in RSR-13-treated dogs(P = not significant).Pti_O2 was30-40% higher in the RSR-13-treated group at anyO₂above critical but did not differ between groups below criticalO₂.Perfusion heterogeneity and convergence of the dissociation curvesnear criticalO₂ may have mitigated any effect of increasedP₅₀ onO₂ diffusion. Still, increasingP₅₀ by 12 Torr with RSR-13significantly increased Pti_O2 atO₂values above critical.

     

Inspiratory-resistive loading increases the ventilatory response to arousal but does not reduce genioglossus muscle activity on the return to sleep

Arousals from sleep are thought to predispose to obstructive sleep apnea by causing hyperventilation and hypocapnia, which reduce airway dilator muscle activity on the return to sleep. However, prior studies of auditory arousals have not resulted in reduced genioglossus muscle activity [GG-electromyogram (EMG)], potentially because airway resistance prior to arousal was low, leading to a small ventilatory response to arousal and minimal hypocapnia. Thus we aimed to increase the ventilatory response to arousal by resistive loading prior to auditory arousal and determine whether reduced GG-EMG occurred on the return to sleep. Eighteen healthy young men and women were recruited. Subjects were instrumented with a nasal mask with a pneumotachograph, an epiglottic pressure catheter, and intramuscular GG-EMG electrodes. Mask CO(2) levels were monitored. Three- to 15-s arousals from sleep were induced with auditory tones after resting breathing (No-Load) or inspiratory-resistive loading (Load; average 8.4 cmH(2)O·l(-1)·s(-1)). Peak minute ventilation following arousal was greater after Load than No-Load (mean ± SE; 8.0 ± 0.6 vs. 7.4 ± 0.6 l/min, respectively). However, the nadir end tidal partial pressure of CO(2) did not differ between Load conditions (43.1 ± 0.6 and 42.8 ± 0.5 mmHg, respectively), and no period of reduced GG activity occurred following the return to sleep (GG-EMG baseline, minimum after Load and No-Load = 2.9 ± 1.2%, 3.1 ± 1.3%, and 3.0 ± 1.3% max, respectively). These findings indicate that the hyperventilation, which occurs following tone-induced arousal, is appropriate for the prevailing level of respiratory drive, because loading did not induce marked hypocapnia or lower GG muscle activity on the return to sleep. Whether similar findings occur following obstructive events in patients remains to be determined.     

Deficiency of the mitochondrial electron transport chain in muscle does not cause insulin resistance

Background

It has been proposed that muscle insulin resistance in type 2 diabetes is due to a selective decrease in the components of the mitochondrial electron transport chain and results from accumulation of toxic products of incomplete fat oxidation. The purpose of the present study was to test this hypothesis.

Methodology/Principal Findings

Rats were made severely iron deficient, by means of an iron-deficient diet. Iron deficiency results in decreases of the iron containing mitochondrial respiratory chain proteins without affecting the enzymes of the fatty acid oxidation pathway. Insulin resistance was induced by feeding iron-deficient and control rats a high fat diet. Skeletal muscle insulin resistance was evaluated by measuring glucose transport activity in soleus muscle strips. Mitochondrial proteins were measured by Western blot. Iron deficiency resulted in a decrease in expression of iron containing proteins of the mitochondrial respiratory chain in muscle. Citrate synthase, a non-iron containing citrate cycle enzyme, and long chain acyl-CoA dehydrogenase (LCAD), used as a marker for the fatty acid oxidation pathway, were unaffected by the iron deficiency. Oleate oxidation by muscle homogenates was increased by high fat feeding and decreased by iron deficiency despite high fat feeding. The high fat diet caused severe insulin resistance of muscle glucose transport. Iron deficiency completely protected against the high fat diet-induced muscle insulin resistance.

Conclusions/Significance

The results of the study argue against the hypothesis that a deficiency of the electron transport chain (ETC), and imbalance between the ETC and β-oxidation pathways, causes muscle insulin resistance.     

Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance

We aimed to investigate the role of betaine supplementation on muscle phosphorylcreatine (PCr) content and strength performance in untrained subjects. Additionally, we compared the ergogenic and physiological responses to betaine versus creatine supplementation. Finally, we also tested the possible additive effects of creatine and betaine supplementation. This was a double-blind, randomized, placebo-controlled study. Subjects were assigned to receive betaine (BET; 2?g/day), creatine (CR; 20?g/day), betaine plus creatine (BET?+?CR; 2?+?20?g/day, respectively) or placebo (PL). At baseline and after 10?days of supplementation, we assessed muscle strength and power, muscle PCr content, and body composition. The CR and BET?+?CR groups presented greater increase in muscle PCr content than PL (p?=?0.004 and p?=?0.006, respectively). PCr content was comparable between BET versus PL (p?=?0.78) and CR versus BET?+?CR (p?=?0.99). CR and BET?+?CR presented greater muscle power output than PL in the squat exercise following supplementation (p?=?0.003 and p?=?0.041, respectively). Similarly, bench press average power was significantly greater for the CR-supplemented groups. CR and BET?+?CR groups also showed significant pre- to post-test increase in 1-RM squat and bench press (CR: p?=?0.027 and p?<?0.0001; BET?+?CR: p?=?0.03 and p?<?0.0001 for upper- and lower-body assessments, respectively) No significant differences for 1-RM strength and power were observed between BET versus PL and CR versus BET?+?CR. Body composition did not differ between the groups. In conclusion, we reported that betaine supplementation does not augment muscle PCr content. Furthermore, we showed that betaine supplementation combined or not with creatine supplementation does not affect strength and power performance in untrained subjects.     

Harvesting surface vegetation does not impede self‐recovery of Sphagnum peatlands

Ecosystem restoration frequently involves the reintroduction of plant material in the degraded ecosystem. When there are no plant nurseries or seeds available on the market, the plant material has to be harvested in the wild, in a “donor ecosystem.” A comprehensive assessment of donor ecosystem recovery is lacking, especially for Sphagnum‐dominated donor peatlands, where all top vegetation is harvested mechanically with different practices. We aimed to evaluate (1) the regeneration of vegetation, especially of Sphagnum mosses, to determine which harvesting practices are best to enhance recovery and (2) the influence of the site hydrological conditions and meteorological variables of the first complete growing season postharvesting on peat moss regeneration. Twenty‐five donor sites covering a 17‐year chronosequence (harvested 1–17 years ago) were inventoried along with 15 associated natural reference sites located in Quebec, New Brunswick, and Alberta, Canada. All donor sites aged 10 years or more were dominated by Sphagnum mosses, though plant composition varied between donor and their associated reference sites because of the wetter conditions at harvested donor sites. Harvesting practices strongly influenced donor site recovery, showing that the skills of the practitioner are an essential ingredient. Harvesting practices minimizing donor site disturbances are recommended, such as the choice of the adequate donor site (localization, hydrologic conditions, vegetation), the use of less disruptive methods, and harvesting when the soil is deeply frozen. This study demonstrated that harvesting surface plant material for peatland restoration is not detrimental towards the recovery of near‐natural peatland ecosystems.     

AMPK stimulation increases LCFA but not glucose clearance in cardiac muscle in vivo

AMP-activated protein kinase (AMPK) independently increases glucose and long-chain fatty acid (LCFA) utilization in isolated cardiac muscle preparations. Recent studies indicate this may be due to AMPK-induced phosphorylation and activation of nitric oxide synthase (NOS). Given this, the aim of the present study was to assess the effects of AMPK stimulation by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 10 mg.kg(-1).min(-1)) on glucose and LCFA utilization in cardiac muscle and to determine the NOS dependence of any observed effects. Catheters were chronically implanted in a carotid artery and jugular vein of Sprague-Dawley rats. After 4 days of recovery, conscious, unrestrained rats were given either water or water containing 1 mg/ml nitro-L-arginine methyl ester (L-NAME) for 2.5 days. After an overnight fast, rats underwent one of four protocols: saline, AICAR, AICAR + L-NAME, or AICAR + Intralipid (20%, 0.02 ml.kg(-1).min(-1)). Glucose was clamped at approximately 6.5 mM in all groups, and an intravenous bolus of 2-deoxy-[(3)H]glucose and [(125)I]-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid was administered to obtain indexes of glucose and LCFA uptake and clearance. Despite AMPK activation, as evidenced by acetyl-CoA carboxylase (Ser(221)) and AMPK phosphorylation (Thr(172)), AICAR increased cardiac LCFA but not glucose clearance. L-NAME + AICAR established that this effect was not due to NOS activation, and AICAR + Intralipid showed that increased cardiac LCFA clearance was not LCFA-concentration dependent. These results demonstrate that, in vivo, AMPK stimulation increases LCFA but not glucose clearance by a NOS-independent mechanism.     

Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance.

This study investigated creatine supplementation (CrS) effects on muscle total creatine (TCr), creatine phosphate (CrP), and intermittent sprinting performance by using a design incorporating the time course of the initial increase and subsequent washout period of muscle TCr. Two groups of seven volunteers ingested either creatine [Cr; 6 x (5 g Cr-H(2)O + 5 g dextrose)/day)] or a placebo (6 x 5 g dextrose/day) over 5 days. Five 10-s maximal cycle ergometer sprints with rest intervals of 180, 50, 20, and 20 s and a resting vastus lateralis biopsy were conducted before and 0, 2, and 4 wk after placebo or CrS. Resting muscle TCr, CrP, and Cr were unchanged after the placebo but were increased (P < 0.05) at 0 [by 22.9 +/- 4.2, 8.9 +/- 1.9, and 14.0 +/- 3.3 (SE) mmol/kg dry mass, respectively] and 2 but not 4 wk after CrS. An apparent placebo main effect of increased peak power and cumulative work was found after placebo and CrS, but no treatment (CrS) main effect was found on either variable. Thus, despite the rise and washout of muscle TCr and CrP, maximal intermittent sprinting performance was unchanged by CrS.     

Aminophylline increases submaximum power but not intrinsic velocity of shortening of frog muscle.

We hypothesized that methylxanthines, such as aminophylline, increase the power developed by submaximally activated frog skeletal muscles by increasing the force developed at any given velocity of shortening. Frog semitendinosus muscles were excised and tested at 20 degrees C in oxygenated control and aminophylline Ringer solutions. Force-velocity relationships were determined and power was calculated from muscles stimulated at frequencies of 80 and 300 Hz. The 300-Hz frequency of stimulation produced a maximum rate of force development. In 50 and 500 microM aminophylline, twitch force increased by 25 +/- 12 and 75 +/- 13%, respectively. Aminophylline did not affect maximum isometric force generation or the shortening velocity at any relative load. At 80-Hz stimulation and in the presence of 500 microM aminophylline, power increased by an average of 11% at 10 of 14 relative loads. At maximum frequencies of stimulation, aminophylline had no effect on any measured parameter. We conclude that aminophylline increases the power developed by submaximally activated frog muscles through an increase in the force generated particularly at the lower velocities of shortening.     

Nandrolone decanoate does not enhance training effects but increases IGF-I mRNA in rat diaphragm.

To examine whether concomitant anabolic steroid treatment combined with training might enhance previously observed training effects (A. Bisschop, G. Gayan-Ramirez, H. Rollier, R. Gosselink, R. Dom, V. de Bock, and M. Decramer. Am. J. Respir. Crit. Care Med. 155: 1583-1589, 1997) and whether insulin-like growth factor I (IGF-I) was involved in these changes, male and female rats were submitted to inspiratory muscle training (IMT) for 8 wk (30 min/day, 5 times/wk) and were compared with untrained controls. During the last 5 wk of training, trained rats were divided to receive weekly either low-dose (LD; 1.5 mg/kg) or high-dose (HD; 7.5 mg/kg) nandrolone decanoate or saline for the IMT and control rats. In both sexes, diaphragm muscle mass and contractile properties were unchanged with treatment. In males, HD resulted in decreased diaphragm type I cross-sectional area (-15%; P < 0.05, HD vs. IMT), whereas no changes were observed in females. Finally, an increase in IGF-I mRNA levels was present in HD male (+73%; P < 0.05, HD vs. IMT) and female treated rats [LD (+58%) and HD (+96%) vs. IMT; P < 0.001]. We conclude that administration of nandrolone decanoate did not enhance the previously observed training effects in rat diaphragm, although it increased the IGF-I mRNA expression levels.     

NMDA-, but not kainate- or quisqualate-dependent increases in cerebellar cGMP are dependent upon monoaminergic innervation.

As previously reported, intracerebellar injections of D-serine, quisqualate and kainate elevated mouse cerebellar cGMP levels. Similarly, activation of endogenous excitatory amino acid utilizing neurons with harmaline or pentylenetetrazole also increased cerebellar cGMP. We previously have demonstrated that the harmaline- and pentylenetetrazol-dependent cGMP increases are NMDA receptor mediated. In this report we further demonstrate that NMDA-dependent increases in cGMP are dependent upon monoaminergic innervation of the cerebellum, while kainate- and quisqualate-dependent cGMP increases are independent of such innervation.     

Heparin increases mRNA levels of thrombospondin but not fibronectin in human vascular smooth muscle cells

The effects of heparin (180 micrograms/ml) on steady state mRNA levels for fibronectin, thrombospondin, actin and collagen types I and III were investigated in human umbilical artery smooth muscle cells. Heparin caused a 120% increase in thrombospondin mRNA levels and a 60% and 180% increase in the mRNA levels of procollagen chains alpha 2(I) and alpha 1(III), respectively. No change in fibronectin or actin mRNA levels resulted from heparin treatment. We reported earlier (Biochem. Biophys. Res. Comm. 148:1264, 1987) that heparin increases smooth muscle cell synthesis of both fibronectin and thrombospondin. These data show that heparin coordinately regulates thrombospondin mRNA and protein levels. The heparin induced increase in fibronectin biosynthesis apparently reflects control at the translational or post-translational level.