In order to investigate the correlation between traumatic servity and blood cAMP and cGMP levels in the patients with acute trauma and its clinical significance, 120 cases of trauma were randomly selected and divided into 4 groups (n = 30 in each group): mildly traumatic group (ISS < or = 9), moderately traumatic group (ISS = 10-16), severely traumatic group (ISS = 17-25) and dangerously traumatic group (> 25). The cAMP and cGMP levels were assayed in sera, leucocytes and platelets respectively in 6 h and 24 h after trauma. The results showed that cAMP and cGMP levels were elevated significantly in sera and platelets (P < 0.05 or P < 0.01), meanwhile cGMP levels in leucocytes (P < 0.05). It was concluded that cAMP and cGMP might play an important role in traumatic stress, participate in the cellular signal transducation and promote the immune function of leucocytes and the coagulation founction of platelets. Serum cAMP and cGMP levels were upregulated correspondingly as ISS increased, and positively correlated to the traumatic severity.
Blood Platelets/metabolism ; Cyclic AMP/*blood ; Cyclic GMP/*blood ; *Injury Severity Score ; Leukocytes/metabolism ; Wounds and Injuries/*blood

This study was designed to investigate the cardiovascular effects of sulfur dioxide (SO₂) in the caudal ventrolateral medulla (CVLM) of anesthetized rats and its mechanism. Different doses of SO₂ (2, 20, 200 pmol) or artificial cerebrospinal fluid (aCSF) were injected into the CVLM unilaterally or bilaterally, and the effects of SO₂ on blood pressure and heart rate of rats were observed. In order to explore the possible mechanisms of SO₂ in the CVLM, different signal pathway blockers were injected into the CVLM before the treatment with SO₂ (20 pmol). The results showed that unilateral or bilateral microinjection of SO₂ reduced blood pressure and heart rate in a dose-dependent manner (P < 0.01). Moreover, compared with unilateral injection of SO₂ (2 pmol), bilateral injection of 2 pmol SO₂ produced a greater reduction in blood pressure. Local pre-injection of the glutamate receptor blocker kynurenic acid (Kyn, 5 nmol) or soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 pmol) into the CVLM attenuated the inhibitory effects of SO₂ on both blood pressure and heart rate. However, local pre-injection of nitric oxide synthase (NOS) inhibitor N^G-Nitro-L-arginine methyl ester (L-NAME, 10 nmol) only attenuated the inhibitory effect of SO₂ on heart rate but not blood pressure. In conclusion, SO₂ in rat CVLM has cardiovascular inhibitory effects, and its mechanism is related to the glutamate receptor and NOS/cGMP signal pathways.
Animals ; Rats ; Heart Rate ; Sulfur Dioxide ; Blood Pressure ; Cyclic GMP ; Receptors, Glutamate

In order to investigate the correlation between traumatic servity and blood cAMP and cGMP levels in the patients with acute trauma and its clinical significance, 120 cases of trauma were randomly selected and divided into 4 groups (n = 30 in each group): mildly traumatic group (ISS < or = 9), moderately traumatic group (ISS = 10-16), severely traumatic group (ISS = 17-25) and dangerously traumatic group (> 25). The cAMP and cGMP levels were assayed in sera, leucocytes and platelets respectively in 6 h and 24 h after trauma. The results showed that cAMP and cGMP levels were elevated significantly in sera and platelets (P < 0.05 or P < 0.01), meanwhile cGMP levels in leucocytes (P < 0.05). It was concluded that cAMP and cGMP might play an important role in traumatic stress, participate in the cellular signal transducation and promote the immune function of leucocytes and the coagulation founction of platelets. Serum cAMP and cGMP levels were upregulated correspondingly as ISS increased, and positively correlated to the traumatic severity.
Adolescent ; Adult ; Blood Platelets ; metabolism ; Cyclic AMP ; blood ; Cyclic GMP ; blood ; Female ; Humans ; Injury Severity Score ; Leukocytes ; metabolism ; Male ; Middle Aged ; Wounds and Injuries ; blood

OBJECTIVETo investigate the effects of catecholamine hormone on the blood and brain of heroin addicts.

METHODSRats were divided into three groups and treated with the glucose (control group), the heroin (im) (heroin group), and the combination of the intramuscular injection of reserpine and heroin (reserpine group). Changes in the levels of the dopamine (DA), cAMP, and cGMP were detected by the radioimmunoassay (RIA) method in the blood and brain tissue.

RESULTSNo significant withdrawal symptoms were observed in the reserpine group. Compared with the control and heroin groups, the blood cAMP levels were increased by 35.36% and 15.53% in the reserpine group, respectively; the cAMP levels in the midbrain ventral tegmental area (VTA), prefrontal cortex (PFC), and hippocampus (Hipp) were increased by 24.08% & 8.53%, 15.66% & 8.13%, and 21.95% & 8.40%, respectively. While compared to the control and heroin groups, the DA levels of the PFC, Hipp, striatum, and nucleus accumbens (NAc) were significantly reduced in the reserpine group, decreasing by 74.09% & 82.86%, 81.06% & 82.23%, 91.62% & 86.55% and 84.35% & 90.63%, respectively. The concentrations of cGMP of the brain tissues in the reserpine group were lower than those in the control group. In addition, the neural electrophysiological testing showed that the electroencephalogram (EEG), electrocardiogram (ECG), and muscle spindle discharge diagram of rats in both the reserpine and heroin groups were apparently changed.

CONCLUSIONCatecholamine hormone plays an important role in heroin addiction.

Animals ; Brain ; drug effects ; metabolism ; Catecholamines ; physiology ; Cyclic AMP ; blood ; metabolism ; Cyclic GMP ; blood ; metabolism ; Dopamine ; blood ; metabolism ; Heroin Dependence ; metabolism ; physiopathology ; Male ; Rats ; Rats, Wistar

OBJECTIVE: To evaluate the therapeutic effect of the combined treatment with balance acupuncture therapy and exercise re-learning rehabilitation therapy and the impact on serum cAMP and cGMP in the patients with hemiplegia of cerebral ischemic stroke. METHODS: A total of 90 patients of hemiplegia of cerebral ischemic stroke were randomized into an observation group and a control group, 45 cases in each one. All of the patients in the two groups received health education, diet guidance, routine symptomatic treatment as well as exercise re-learning rehabilitation therapy. Additionally, in the observation group, balance acupuncture therapy was applied, in which, the acupoints on the aspect of the human body, on the governor vessel and bladder meridian were adopted in the morning and those on the aspect of the human body, on the conception vessel and kidney meridian were stimulated in the afternoon. In the control group, the regular acupuncture was given. In the two groups, both acupuncture and rehabilitation therapies were given 5 days a week, 2 week-treatment as one course and totally 2 courses were required. Separately, before and after treatment, the score of Fugl-Meyer assessment (FMA) and the score of Chinese stroke scale (CSS) were recorded, the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) detected in serum and the clinical therapeutic effect were evaluated in the two groups. RESULTS: After treatment, FMA score was increased in the patients of either of the groups as compared with that before treatment (<0.01) and CSS score decreased as compared with that before treatment (<0.01). After treatment, FMA score in the observation group was higher than that in the control group (<0.01) and CSS score was lower than the control group (<0.01). After treatment, the level of serum cAMP of the patients in either of the groups was increased as compared with that before treatment (<0.01) and that of cGMP decreased as compared with that before treatment (<0.01). After treatment, the level of cAMP in the observation group was higher than that in the control group (<0.01) and that of cGMP was lower than the control group (<0.01). The total effective rate was 93.3% (42/45) in the observation group, better than 73.3% (33/45) in the control group (<0.01). CONCLUSION The balance acupuncture therapy combined with exercise re-learning rehabilitation effectively improves the motor function of the affected limb, relieves injury and regulate the levels of serum cAMP and cGMP in the patients with hemiplegia of ischemic stroke.
Acupuncture Points ; Acupuncture Therapy ; Brain Ischemia ; therapy ; Cyclic AMP ; blood ; Cyclic GMP ; blood ; Hemiplegia ; therapy ; Humans ; Stroke ; therapy ; Stroke Rehabilitation ; Treatment Outcome

OBJECTIVETo investigate the effects of external counterpulsation (ECP) on shear stress and signal transduction in canines with myocardial infarction.

METHODSNineteen healthy dogs were randomly divided into control, ischemia, and ischemia plus ECP groups. Myocardial infarction was induced in the latter two groups by ligation of the left anterior descending artery (LAD). Serum and aorta NO levels of the dogs were determined by modified nitrate reductase method, and serum and aorta cyclic guanosine monophosphate (cGMP) levels by radioimmunoassay.

RESULTSThe shear stress in the truncus brachiocephalicus decreased after LAD ligation, but increased significantly after 2 h of ECP treatment. Serum and aorta NO levels in ECP and control groups were significantly higher than those in the ischemic group (P<0.05). Serum and aorta cGMP levels in control group and ECP group after LAD ligation were also significantly higher than those in the ischemic group (P<0.05).

CONCLUSIONECP can increase the shear stress and increase NO and cGMP levels in dogs with myocardial ischemia, which might be an important mechanism of ECP for protection of the ischemic myocardium.

Animals ; Aorta ; Counterpulsation ; Cyclic GMP ; blood ; metabolism ; Dogs ; Female ; Male ; Myocardial Infarction ; blood ; metabolism ; surgery ; Nitric Oxide ; blood ; metabolism ; Radioimmunoassay ; Stress, Mechanical

OBJECTIVETo investigate the dynamics of plasma cAMP/cGMP in patients during cardiac surgery, and its relationship to traumatic stress.

METHODSSixteen patients, aged 19.31 years+/-10.4 years, who underwent an open heart operation with cardiopulmonary bypass (CPB) and hypothermia were served as subjects. The arterial plasma concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured by radioimmunoassay 2 hours before operation, after heparinization, 20 minutes following CPB, at the end of the operation, and 24 and 72 hours postoperatively, respectively. The patients' preoperative blood samples were heparinized and the venous blood samples of 30 healthy blood donors were taken to measure the levels of cAMP and cGMP as heparin and normal controls separately.

RESULTSThere were no statistical difference among the heparin control, preoperative level and normal control. The peak values of cAMP and cGMP occurred during CPB and plasma cAMP levels changed synchronously with intensities of operative stimulus to human body. However cGMP level was mainly related to the operative stimulus to the heart and CPB. The cAMP value was positively correlated with the cGMP value (r=0.6313, P<0.001).

CONCLUSIONSDynamic variation of plasma cyclic ribonucleotide can be considered as a reference parameter for intensity of traumatic stress.

Adolescent ; Adult ; Biomarkers ; analysis ; Cardiopulmonary Bypass ; Coronary Disease ; blood ; surgery ; Cyclic AMP ; analysis ; blood ; Cyclic GMP ; analysis ; blood ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Postoperative Period ; Preoperative Care ; Radioimmunoassay ; Reference Values ; Sensitivity and Specificity ; Stress, Psychological ; blood

The characteristics of an ideal intravenous anesthetic agent include stability in solution, rapid onset of action, minimal effect on the cardiovascular and respiratory systems, short elimination half life, and minimal side effects. Using this criteria, the ultra-short acting barbiturate, thiopental has long been considered the gold standard of intravenous agents used for induction of anesthesia. In normovolemic subjects, thiopental produces a transient decrease in blood pressure, and increase in heart rate. In practice, thiopental is administered high dose(30 mg/kg IV) for brain protection, rarely. We tried to confirm the direct vascular effects of thiopental and its mechanism on the rabbit abdominal aorta in vitro. The rabbit abdominal aorta were precontracted with norepinephrine(10(-7) M) in 5 ml tissue bath and 10(-5), 10(-4), and 10(-3) M thiopental was administrated in cumulative manner. Ten minutes later, changes of the vascular tones were obtained. For confirming the relaxing mechanism induced by thiopental, experiment was performed by indomethacin, methylene blue and LNAME pretreatment, and endothelium removed, respectively. The results were as follows 1) Thiopental at 10(-5), and 10(-4) M produced no signifcant changes, and at 10(-3) M produced signifcant relaxation. 2) There were no significalnt difference in their vascular tones between intact and denuded endothelium group. 3) The vascular tones were not affected by LNAME, methylene blue, and indomethacin pretreatment. These results suggest that thiopental induce vasorelaxation in rabbit abdominal aorta at high concentration(10(-3) M). The vasorelaxation mechanism is not correlated with NO, cyclic GMP, prostacyclin and endothelium.
Anesthesia ; Aorta, Abdominal* ; Baths ; Blood Pressure ; Brain ; Cyclic GMP ; Endothelium ; Epoprostenol ; Half-Life ; Heart Rate ; Indomethacin ; Methylene Blue ; Relaxation ; Respiratory System ; Thiopental* ; Vasodilation

BACKGROUND: The diagnostic and prognostic implication of exaggerated blood pressure response to exercise has not been well characterized. Endothelial dysfunction has been demonstrated in patients with atherosclerosis or with risk factors for coronary artery disease. However, whether the cause of exercise induced hypertension might be due to endothelial dysfunction has not been well elucidated. Therefore, we designed this study to evaluate the endothelial function in patients with exaggerated blood pressure response during exercise. METHODS: Exercise hypertension is defined as a systolic blood pressure >or= 210 mmHg in men and >or= 190 mmHg in female, during treadmill exercise test. The endothelial function of the brachial artery, in 35 patients with exercise hypertension and 35 control subjects (mean age of 45.5+/-8.1) were measured by a high resolution ultrasound technique. The concentrations of nitrite and cyclic-GMP were measured from exercise hypertension group and control subjects during, before and after treadmill exercise. RESULTS: There were no significant differences in the clinical variables between the control and exercise hypertension group. The LVH on ECG was detected more frequently in exercise hypertension group (14 % vs. 40 %, p<0.05) and LV mass/BSA (132+/-12 vs. 139+/-14 g/m2, p<0.05) was also higher in exercise hypetension group. Endothelial-dependent vasodilation was impaired in patients with exercise hypertension (6.5+/-0.8 vs. 3.1+/-0.6 %, p<0.05). On univariate analysis, the extent of vasodilation was significantly correlated with age (r=-0.28, p<0.05) and delta systolic blood pressure (r=-0.36, p<0.05). Both the levels of NO2-/NO3- and cyclic-GMP at the maximal exercise were significantly higher than those at rest and recovery in control and exercise hypertension group (p<0.05). Although there was no difference at the increment of NO2-/NO3- during the maximal exercise between the control and exercise hypertension group (55+/-17 vs. 56+/-12 mmHg, p>0.05), a significant difference of cyclic GMP level during the maximal exercise was noted between the groups (10+/-1.8 vs. 8.3+/-2.5 pmol/mL, p<0.05). CONCLSUION: Patients with exercise induced hypertension have impaired endothelium-dependent vasodilation. This study supports the concept that endothelial dysfunction may play a significant role in exercise induced hypertension.
Atherosclerosis ; Blood Pressure* ; Brachial Artery ; Coronary Artery Disease ; Cyclic GMP ; Electrocardiography ; Endothelium ; Exercise Test* ; Female ; Humans ; Hypertension ; Male ; Nitric Oxide ; Risk Factors ; Ultrasonography ; Vasodilation

This study was designed to investigate inhibitory effects and possible mechanisms of snake venom tripeptide (pENW) on platelet adhesion in order to promote the development of a novel anti-platelet therapy. To study the inhibitory effects of pENW on platelet adhesion, washed platelets pre-incubated with pENW (116.5-466.2 μmol x L(-1)) were used to test the ability of platelet adhesion to fibrinogen. Effect of pENW on fibrin clot retraction was also tested. Effect of pENW on platelets viability was tested by MTT assay. Effect of pENW on reactive-oxygen species (ROS) levels of platelet was studied by flow cytometry assay. Calcium mobilization in Fura-2/AM-loaded platelets was monitored with a spectrofluorimeter. Cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), thromboxane A2 (determined as its metabolite thromboxane B2) were measured using enzyme immunoassay kits. Akt, ERK and p38 phosphorylation were tested by Western blot. The results showed that pENW inhibited platelet adhesion and fibrin clot retraction in a concentration-dependent manner without cytotoxicity. Intracellular cGMP and cAMP in both resting and thrombin-activated platelets were increased by pENW. In addition, pENW attenuated intracellular Ca2+ mobilization and TXA2 production in platelets stimulated by thrombin. As shown by Western blot assay, Akt, ERK and p38 phosphorylation in thrombin-induced platelet were attenuated by pENW. However, inhibitory effects of pENW had nothing to do with ROS. Thus, pENW exhibited a significant inhibition on platelet adhesion to fibrinogen, which means pENW could block the first step of thrombosis as while as retard the more stable clot formation. The mechanisms of pENW on inhibition platelet adhesion might be related to instant regulations, such as protein kinases.
Blood Platelets ; drug effects ; Blotting, Western ; Calcium ; metabolism ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Flow Cytometry ; Phosphorylation ; Platelet Aggregation ; drug effects ; Reactive Oxygen Species ; metabolism ; Snake Venoms ; chemistry ; Thromboxane A2 ; metabolism ; Thromboxane B2 ; metabolism