eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
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2006-04
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1
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article
Editorial Committee
http://ppj.phypha.ir/article-1-62-en.pdf
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
24765236
24765244
2006-04
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3
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article
Sex differences and role of gonadal hormones in development of tolerance to morphine analgesia and glutamate level in the nucleus accumbens of rats: A microdialysis study
Seyede Zahra Mosavi
1
Bijan Shafaghi
2
Farzad Kobarfard
3
Masoumeh Jorjani
4
Introduction: Sex differences are observed in the development of tolerance to antinociceptive effect of
opioid drugs such as morphine, but the underlying mechanisms remain unclear. Critical role of glutamate in
the development and maintenance of opioid tolerance has been reported by many investigators. There are also
evidences about interaction between gonadal hormones and neuromodulatory systems including opioidergic and
glutamatergic systems. The present study examined the sex differences and role of gonadal hormones on the
glutamate level in the nucleus accumbens in morphine tolerant rats using in vivo microdialysis.
Methods: Intact, gonadectoized and sham-operated male and female rats were used. Morphine (7 mg/kg/day,
SC) was administered for 8 days. Response to thermal noxious stimuli were measured by tail-flick test. Tolerance
was defined as the response which was not significantly different from baseline.
Results: The results showed that after chronic morphine administration, antinociceptive tolerance in male
rats was significantly greater than females (P<0.05). Sex differences in morphine tolerance disappeared with
gonadectomy of animals. There was also significant sex difference in glutamate level in nucleus accumbens of
morphine tolerant rats (P<0.05), Glutamate level was decreased after ovariectomy of female rats (P<0.05), but
gonadectomy had not significantly effect on glutamate level in males.
Conclusion: Results of this study provide evidence of sex differences in development of tolerance to morphine
in rats and mediatory roles of gonadal hormones and glutamate levels in these differences.
http://ppj.phypha.ir/article-1-80-en.pdf
Sex differences
Morphine antinociception tolerance
Glutamate
Microdialysis
Tail flick test
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
24765236
24765244
2006-04
10
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19
article
Induction of Human Embryonic Stem Cells into neuronal differentiation by increasing cyclic Adenosine Mono Phosphate
Hossein Baharvand
1
Bijan Hatami
2
Mohammad Massumi
3
Introduction: To evaluate the cAMP -mediated IBMX (3-IsoButyle -1-Methyl Xanthin) and db-cAMP
(dibutyryl cAMP) effects on differentiation of human Embryonic Stem Cells (hESCs) into nerve cells were the
objectives of this study.
Methods: We have used Royan H1 hESC- derived embryoid bodies with four treatment groups: six days
treatment with IBMX (5×10 -4M) and db-cAMP (10 -9M) (referred to as cAMP), retinoic acid (RA, 10 -6M),
IBMX + db-cAMP + RA, and control (no treatment). Immunocytochemistry was carried out for neural specific
antibodies including β-Tubulin III, Microtubule Associated Protein 2 (MAP-2), Neurofilament Protein-Heavy
chain (NF-H), Glial Fibrilary Acidic Protein (GFAP) and Synaptophysin as well as morphological studies. Semiquantitative
RT-PCR was also used to evaluate gene expression involved in neurogenesis.
Results: In the 4+6+4 days the neuronal process were apparently observed. Immunocytochemical studies using
nerve specific antibodies for proteins such as β- Tubulin III, MAP-2, NF-H, GFAP and Synaptophysin showed
the presence of these neuronal and astrocyte markers in differentiated cells by cAMP. Evaluation of expression
of genes involved in neurogenesis showed that Hash1, Synaptophysin, β-Adrenergic Receptor and Acetylcholine
Receptor- which were silent in embryoid bodies - switched on after treatment with cAMP and/or RA. Relative
expression of nerve specific genes showed a significant enhancement in expression of Synaptophysin, NFM and
β-Adrenergic Receptor during differentiation, which, with the enhancement in cAMP treated groups were more
than those treated with RA and control (p < 0.05).
Conclusion: In conclusion, this study showed that cAMP could be a neurogenic agent for human embryonic
stem cells differentiation.
http://ppj.phypha.ir/article-1-81-en.pdf
Embryonic stem cells
cAMP
Neurogenesis.
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
24765236
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2006-04
10
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article
The effects of chronic oral administration of verapamil on thyroid function in rat
Mohammad Shabani
1
Saleh Zahedi Asl
2
Homa Manaheji
3
Introduction: Verapamil, a phenylalkylamin –type Ca2+ channel blocker, is widely used in the treatment of
cardiovascular disorders especially as an antiaryhthmic and antiangina agent. Theoretically, calcium can influence
thyroid function and there are evidences that Ca2+ channel blockers are able to interfere with thyroid function. In
this study, the effects of chronic oral administration of verapamil on thyroid function of male Wistar rats were
investigated.
Methods: Study was performed on 5 groups of animals groups 1 to 3 were treated with verapamil at doses of
10, 20 and 50 mg /kg respectively for two months via oral tube. Sham group received only distilled water, while
control group received neither verapamil nor distilled water. At the end of this period animals were anaesthetized,
abdomen was opened and blood samples were obtained from abdominal aorta. The samples were centrifuged sera
were separated and stored at – 20 ◦C until the time of the assays. Total triiodothyronine (TT3), total thyroxin (TT4),
free triiodothyronine (FT3) and free thyroxin (FT4), T3 uptake levels were assayed by ELISA (DRG). Thyroid
stimulating hormone (TSH) was determined by radioimmunoassay using DRG kits.
Results: Total T4 level was significantly lower in sham (3.49 ± 0.1μg/dl) and verapamil dose 10 mg /kg
(3.6±0.14) groups than in control group (4.5±0.34), while it was significantly higher in verapamil 50 mg /kg
(4.24±0.2) group as compared to the sham group. Total T3 concentration in verapamil 20 mg /kg group (62±8.9ng/
dl) was decreased significantly compared to the control group (103.3±14). Free T3 and free T4 were significantly
lower in sham group (p<0.005) compared to control group, while it was increased in verapamil groups of 20
and 50 mg /kg compared to sham group. Level of T3 up-take was decreased significantly (p<0.005) in sham
(20.97±1.49%) and verapamil 20 (20.7±1.4) mg /kg compared to control group (27.6±1), while it was higher
in verapamil 10 and 50 mg /kg groups than sham group. Thyroid stimulating hormone levels were similar in all
groups. There were no significant differences in the T3/T4 ratio and body weights on first and last day of the groups
compared to control group.
Conclusion: It can be concluded that long term oral administration of verapamil doesn’t have inhibitory effect
on thyroid function, however it can block adverse effect of handling stress on thyroid function. Therefore, from
thyroid function point of view, the drug can be used safely for the duration of this study.
http://ppj.phypha.ir/article-1-73-en.pdf
verapamil
thyroid function
long term
rats.
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
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2006-04
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article
Forskolin attenuates the paraoxon-induced hyperexcitability in snail neurons
Jafar Vatanparast
1
Mahyar Janahmadi
2
Houri Sepehri
3
Ali Haeri-Rohani
4
Ali Reza Asgari
5
Introduction: Since organophosphorus compounds (OP) are toxic and designed to destroy insects and pest
species, there are many hazards associated with their use. Although, the main target site of these compounds is
acetylcholinesterase (AChE), however it has become increasingly evident that OPs have also other direct effects
on cellular processes. In the present study, the effects of low concentrations of paraoxon and its interaction with
forskolin, an activator of protein kinase A (PKA), were studied on Ca2+ spike configuration and frequency in
neurons of snail Caucasotachea atrolabiata.
Methods: Subesophageal ganglia neurons were recorded in current clamp mode in Na+ free Ringer solution
that contained voltage dependent potassium channel blockers, 4AP and TEA.
Results: Paraoxon (0.3-0.6 μM) decreased the duration of spontaneous Ca2+ spikes. This effect was seen with a
suppression of single spike AHPs, leading to an increment in firing rate. Paraoxon induced hyperactivity appeared
to be a consequence of decrease in Ca2+ influx during spikes which is the main determinant of AHP duration by
activating Ca2+ dependent potassium channels. Forskolin (25 μM), in the absence of a significant change in spike
duration, decreased the duration of single spike AHPs and increased the frequency of spikes. After forskolin
application, paraoxon decreased the duration of Ca2+ spikes and AHPs, and increased the activity. However, these
effects, especially on spike duration, were not as pronounced as in the absence of forskolin.
Conclusion: These findings suggest that although forskolin, similar to paraoxon, decreases the AHP and
increases the frequency of spikes but it employs mechanism(s) different from paraoxon which also oppose the
effects of paraoxon on Ca2+ spikes configuration and frequency.
http://ppj.phypha.ir/article-1-74-en.pdf
Paraoxon
Forskolin
Ca2+ spike
Neuronal activity
Snail.
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
24765236
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2006-04
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article
The effects of deprenyl on P75 receptor mRNA changes in new born rats after sciatic nerve axotomy
Taghi Tiraihi
1
hesam Amini
2
Seyed Javad Mowla
3
Marjan Heshmati
4
Introduction: Neurotrophins belong to growth factor family and their function is based on their receptors.
They bind two types of receptors: p75 and tyrosine kinase. The motoneuron survival or death depends upon
the neurotrophic factors. Recent studies have demonstrated that axotomy in peripheral nerve induces apoptosis
of motoneuron. Deprenyl or Selegiline is known as a drug with neuroprotective effect on motoneurons. In this
investigation, we evaluated mRNA changes in p75 receptor by anti-apoptic effect of deprenyl in motoneuron
death induced by axotomy of rat sciatic nerve.
Methods: The left sciatic nerves of Sprague-Dawley newborn 3 days old rats, were axotomized in the middle
of thigh. The newborn rats were divided into two groups one group was treated with intra peritoneal injection of
2.5 mg/kg deprenyl (treated) and the other group with normal saline (untreated). Each group was divided to 3 sub
groups as, the first was treated with 2.5 mg/kg deprenyl or normal saline one hour before surgical transection, the
second and third were treated at, and one hour after surgery, respectively. Molecular studies for mRNA changes
Trk-B and P75NTR receptor were done on two groups of animals which were sacrificed 4 hours after injection and
other one, 24 hours after injection.
Results: The RT-PCR revealed that deprenyl has reduced the mRNA P75 after 24 hours.
Conclusion: Deprenyl can maintain motoneurons by reducing mRNA P75 receptor.
http://ppj.phypha.ir/article-1-75-en.pdf
Neurotrophin
Deprenyl
Axotomy
Apoptosis
P75 receptor.
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
24765236
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2006-04
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article
Pre-emptive effects of MK-801 and morphine on behavioural responses in experimental chronic constriction sciatic nerve injury in adult male rats
Ghola Ali Hamidi
1
Homa Manaheji
2
Mahyar Janahmadi
3
Mahmood Salami
4
Introduction: Neuropathic pain syndromes are changes resulting from damage to neuronal pathways that
are characterized by spontaneous burning sensation with accompanying allodynia and hyperalgesia. Since the
treatments of neuropathic pain are poorly understood and existing treatments are often ineffective, it is important
to increase our understanding of the neuropathic pain states in order to identify strategies for the development
of effective therapies. The purpose of this study was to investigate the involvement and pre-emptive treatment
of morphine and / or NMDA receptor antagonist MK-801, and co-administration of both drugs on behavioural
responses in an experimental model of neuropathic pain (CCI).
Methods: Experiments were performed on six groups (n=8) of male Sprague-Dawley rats (230-280g). In the
groups that received drugs, two groups were injected with MK-801 (0.3 mg/kg, 20 min before, and 6 h after the
operation) or morphine (8 mg/kg, 30 min prior to the operation). Another group received both drugs with the same
doses and protocols. Finally, one group received normal saline in same volumes. The animals were tested for
allodynia and hyperalgesia reactions at 0, 3, 7, 14, 21 and 28 days after CCI of the sciatic nerve.
Results: Our data revealed that the CCI produces mechanical and cold allodynia and a hypersensitivity to
noxious stimulations. MK-801 and morphine produced only a slight cold anti-allodynic response. On the other
hand, co-injection of morphine and MK-801 markedly reduced cold allodynia at the days 7 (P<0.01), 14 (P<0.05)
and 21 (P<0.05) when compared with the saline group. However, there was slight alleviation of the mechano
allodynia, and, heat- and mechano-hyperalgesia. Results demonstrate that the CCI model importantly influences
the behavioural responses to both the thermal and mechanical stimulations.
Conclusion: We conclude that co-administration of both drugs can be more effective than MK-801 and
morphine administered alone in the induced neuropathic pain.
http://ppj.phypha.ir/article-1-76-en.pdf
Pre-emptive
Neuropathic pain
Allodynia
Hyperalgesia
MK-801
Morphine
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
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2006-04
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56
article
Ascorbic acid antagonizes nicotine-induced place preference and behavioral sensitization in female mice
Ali Akbar Aliabadi
1
Hedayat Sahraei
2
Mehrangiz Sadooghi
3
Hasan Ghoshooni
4
Mehrvaz Alaf-Javadi
5
Seyed Hasan Salimi
6
Amir Abbas Barzegari
7
Introduction: The influence of ascorbic acid on the nicotine-induced conditioned place preference (CPP) and
behavioral sensitization was investigated in the present study.
Methods: In a pilot study, place conditioning and locomotor activity were investigated after nicotine (0.25,
0.5, 0.75, 1, 1.5 and 2 mg/kg) or ascorbic acid (1, 10, 100 and 1000 mg/kg) administration. Different doses of
ascorbic acid in conditioning days or on the test days were used. Behavioral sensitization was induced in animals
by daily intraperitoneal administration of nicotine (0.25 mg/kg) for seven cosecutive days followed by one day
interval. On 9th day, locomotor activity was induced by ineffective dose of nicotine (0.1 mg/kg). Ascorbic acid was
injected 20 min before each injection of nicotine (acquisition of sensitization) or acutely 20 min before a challenge
nicotine injection (expression of sensitization).
Results: The results showed that intraperitoneal nicotine (1 mg/kg) administration can induce place preference
whereas acute administration of the drug induces catalepsy. Administration of ascorbic acid did not induce place
preference nor place aversion and also did not change the locomotor activity. Locomotor sensitization in mice
was produced by intraperitoneal injection of nicotine (0.25 mg/kg) for 7 consecutive days. On the 9th day of
experiments, activity of the mice was recorded after challenge with nicotine (0.1 mg/kg, i.p.). The senisitization
was better achived when the ineffective dose of nicotine (0.1 mg/kg) was applied. Administration with ascorbic
acid reduced both the acquisition and expression of nicotine-induced CPP. It was shown that ascorbic acid
attenuated the acquisition of nicotine sensitization in a dose-independent manner but the expression of nicotineinduced
sensitization was not affected by ascorbic acid.
Conclusion: We conclude that ascorbic acid may interfere with nicotine-induced place preference and
behavioral sensitization.
http://ppj.phypha.ir/article-1-77-en.pdf
Nicotine; Ascorbic acid; Place preference; Behavioral sensitization; Mice.
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
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2006-04
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62
article
Intrathecal administration of epinephrine inhibits and reverses analgesic tolerance to analgesic effect of morphine in rats
Leila Satarian
1
Mohammad Javan
2
Yagoob Fathollahi
3
Introduction: Several researches have reported that stress is able to inhibit the development of morphine
tolerance via activating of Hypothalamic-Pituitary-Adrenal (HPA) axis. In the present study we tried to examine
the effect of epinephrine, the product of adrenal medulla, on the development of morphine tolerance.
Methods: Analgesic tolerance was induced by intrathecal (i.t.) injection of morphine 15 μg/kg, twice a day
for 5 days. To study the effect of epinephrine on morphine tolerance, epinephrine (2, 5, 10 or 20 μg/kg, i.t.) was
administrated 20 minutes before morphine injection. Analgesia was assessed using tail flick test.
Results: In animals that received combined treatments of morphine and epinephrine in doses 2, 5, 10 or 20 μg/
kg for 5 days, at 6th day, morphine produced a more potent analgesia comparing with animals that received saline
and morphine during days 1-5. Following tolerance induction during first 5 days, co-administration of epinephrine
and morphine during days 6 – 10 reduced the initial tolerance as it induced potent analgesia on day 11th.
Conclusion: Our results showed that i.t. administration of epinephrine is able to inhibit and reverse the
analgesic tolerance to morphine. It also suggests the possible role of adrenal medulla and epinephrine in mediating
the inhibitory effect of stress and HPA activation of the development of analgesic tolerance to morphine.
http://ppj.phypha.ir/article-1-78-en.pdf
Tolerance
Morphine
Opioids
Epinephrine.
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
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2006-04
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69
article
Amelioration of rat renal ischemia/reperfusion injury by L-Nil
Maryam Zahmatkesh
1
Mehri Kadkhodaee
2
Hossein Ali Arab
3
Ali Ahadi
4
Introduction: Ischemia/reperfusion (IR) injury involves a complex interrelated sequence of events. High
levels of nitric oxide (NO) are generated with inducible form of nitric oxide synthase (iNOS) leading to the renal
IR injury and glutathione (GSH) depletion. The present study was designed to investigate the effect of L-Nil (N6-
(1-Iminoethyl)-L- lysine.hydrochloride), a selective inhibitor of iNOS, in prevention of renal GSH depletion and
IR injury.
Methods: Ischemia was induced by 40-min clamping of the renal arteries followed by 6 h reperfusion. Rats
were randomly assigned to four groups: Sham operated, Sham- L-Nil, IR and IR- L-Nil. In the IR groups, rats
were administered saline or L-Nil (3 mg/kg iv bolus followed by infusion of 1 mg/kg/h) 15 min prior ischemia.
Other groups underwent surgery protocol but did not undergo renal arteries occlusion and were maintained under
anesthesia for the duration of the experiment (40 min + 6 h). Renal function was assessed by plasma creatinine
(Cr), Blood Urea Nitrogen (BUN), and aspartate aminotransferase (AST) measurements. Fractional excretion of
Na+ (FENa+), urinary N-acetyl-ß-D-glucosaminidase (NAG) activity and renal GSH level were also measured.
Results: We found that L-Nil significantly reduced the IR mediated increases in Cr, BUN, AST, FENa+, NOx and
urine NAG activity.
Conclusion: These results emphasize the multifactorial nature of renal IR injury and the need for a multidrug
therapy in the future.
http://ppj.phypha.ir/article-1-79-en.pdf
Kidney
Ischemia-reperfusion
Nitric oxide synthase
Rat
L-Nil.
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
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2006-04
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article
Study on mechanism of vasorelaxatory effect of Vitis vinifera leaf extract in rat aorta
Mohammad Kazem Gharib Naseri
1
Akbar Heidari
2
Introduction: Our previous studies showed that hydroalcoholic extract of leaf of Vitis vinifera relaxes the
phenylephrine-induced contraction in rat thoracic aorta. This effect was dependent on endothelial integrity and
NO-cGMP system. The vasorelaxant effect of extract was much lesser on KCl-induced contraction. We, therefore,
postulated that K+ channels are involved. The main aim of the present study was to determine the type of K+
channels involved in this vasorelaxant effect.
Methods: Thoracic aorta with intact endothelium was removed from adult male Wistar rats (170-220g).
The aorta was mounted in an organ bath containing Krebs-Henseleit (37 ºC, pH 7.4) bubbled with O2. Aortic
contractions were recorded isometrically under 1 g resting tension. The aorta endothelium was considered intact
if acetylcholine (1 μM) could induce more than 70% aorta relaxation on 1μM phenylephrine-induced contraction.
Extract was prepared by maceration method using 70% alcohol and the solvent was then evaporated.
Results: The results showed that in the presence of tetraethylammonium (10 mM), the vasorelaxant effect of
extract (0.25, 0.5, 1 and 2 mg/ml) was reduced (P<0.001, n=7). In contrast, glibenclamide (1 μM) had no effect.
In calcium-free (plus 0.1 mM of EDTA) Krebs-Henseleit solution, the vasorelaxant effect of extract (0.25, 0.5
and 1 mg/ml) was reduced (P<0.0001, n=8). Furthermore, the vasorelaxant effect of extract was unaffected by
indomethacin (1 μM).
Conclusion: These results suggest that Vitis vinifera leaf hydroalcoholic extract induces relaxation in rat
aorta possibly by opening the Ca2+ -operated K+ channels but, not ATP- sensitive K+ channels and extracellular
calcium was essential for inducing vasorelaxation by extract. Furthermore, cyclooxigenase was not involved in
this vasorelaxant effect.
http://ppj.phypha.ir/article-1-82-en.pdf
Vitis vinifera
Rat
Aorta
K+ channels.
eng
Iranian Society of Physiology and Pharmacology
Physiology and Pharmacology
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24765244
2006-04
10
1
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85
article
Effect of Aerobic Training on Coagulant Activity in Healthy Young Men
Zahra Sadat Rezaeian
1
Giti Torkaman
2
Fatemeh Nad-ali
3
Roya Ravanbod
4
Mostafa Nejatian
5
Babak Gosheh
6
Mohammad Ali Broumand
7
Introduction: Effects of exercise on different body systems, especially cardiovascular and musculoskeletal
systems are evidenced. There is a dynamic homeostatic balance between coagulation and fibrinolysis in normal
circulation. Effect of exercise and training on this homeostatic balance has been studied extensively but there are
a few studies with regards to analysis of the effects of training programs on coagulation factors. Therefore, we
studied the effect of 8 weeks aerobic training program on coagulation factors in healthy young men.
Methods: Subjects were 16 young sedentary men without any history of cardiac, coagulation or respiratory
problems in their first-degree family and their cardiovascular health was confirmed by a cardiac specialist. We
randomly selected 10 of them as test group who participated in a submaximal training program on cycle ergometer
3 times a week for 8 weeks. Each training session consisted of 1 minute warm up, 15 minute aerobic exercise, 8
minute active recovery and 45 minute passive recovery. The remaining individuals were controls and restrained
from exercise in this period. Before and after training period, response of coagulation system to a submaximal
exercise on cycle ergometer was studied by a standardized Ergometery test.
Results: Basic value of coagulation variables were the same in both groups before and after training period.
After 8 weeks, there was no significant change in anthropometric variables in both groups and so the change in
blood variables was independent to physical characteristics of individuals. After 8 weeks of aerobic training,
FVIII:c, FIX:c, Fbg and vwF:ac increased in response to exercise that was statistically significant only in Tr
group. There was a significant decrease in vwF:ag, aPTT, FVII in this group. We conclude that 8 weeks aerobic
training enhances the response of FVIII:c, FIX:c, FVII:c, vwF:ac, Fbg and aPTT to exercise but has no effect on
the response of vwF:ag and PT.
Conclusion: It seems that the recommended aerobic exercise training protocol will enhance the response of
coagulation factors to one session of Ergometric exercise in healthy young men. Due to the importance of blood
homeostasis and the effects of coagulation and fibrinolysis imbalance, any type of physical activity especially any
exercise program should be analyzed carefully for its effect on haemostatic balance.
http://ppj.phypha.ir/article-1-83-en.pdf
aerobic training-cycle ergometer-coagulation-FVIII.